<?xml version="1.0" encoding="US-ASCII" standalone="no"?>
<!--Generated by ThunderDome XBRL - 12:01AM UTC 2018-05-11--><link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all" xlink:type="simple"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member" xlink:type="simple"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain" xlink:type="simple"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension" xlink:type="simple"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-9-accrued-liabilities" xlink:href="clsn-20180331.xsd#statement-note-9-accrued-liabilities" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-9-accrued-liabilities" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AccountsPayableAndAccruedLiabilitiesDisclosureTextBlock" xlink:label="us-gaap_AccountsPayableAndAccruedLiabilitiesDisclosureTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="us-gaap_AccountsPayableAndAccruedLiabilitiesDisclosureTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-4-new-accounting-pronouncements" xlink:href="clsn-20180331.xsd#statement-note-4-new-accounting-pronouncements" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-4-new-accounting-pronouncements" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DescriptionOfNewAccountingPronouncementsNotYetAdopted" xlink:label="us-gaap_DescriptionOfNewAccountingPronouncementsNotYetAdopted" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="us-gaap_DescriptionOfNewAccountingPronouncementsNotYetAdopted" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-2-basis-of-presentation" xlink:href="clsn-20180331.xsd#statement-note-2-basis-of-presentation" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-2-basis-of-presentation" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BasisOfAccounting" xlink:label="us-gaap_BasisOfAccounting" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="us-gaap_BasisOfAccounting" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-1-business-description" xlink:href="clsn-20180331.xsd#statement-note-1-business-description" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-1-business-description" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NatureOfOperations" xlink:label="us-gaap_NatureOfOperations" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="us-gaap_NatureOfOperations" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-document-and-entity-information" xlink:href="clsn-20180331.xsd#statement-document-and-entity-information" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-document-and-entity-information" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_AmendmentFlag" xlink:label="dei_AmendmentFlag" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_CurrentFiscalYearEndDate" xlink:label="dei_CurrentFiscalYearEndDate" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_DocumentFiscalPeriodFocus" xlink:label="dei_DocumentFiscalPeriodFocus" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_DocumentFiscalYearFocus" xlink:label="dei_DocumentFiscalYearFocus" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_DocumentInformationLineItems" xlink:label="dei_DocumentInformationLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_DocumentInformationTable" xlink:label="dei_DocumentInformationTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_DocumentPeriodEndDate" xlink:label="dei_DocumentPeriodEndDate" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_DocumentType" xlink:label="dei_DocumentType" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityCentralIndexKey" xlink:label="dei_EntityCentralIndexKey" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityCommonStockSharesOutstanding" xlink:label="dei_EntityCommonStockSharesOutstanding" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityCurrentReportingStatus" xlink:label="dei_EntityCurrentReportingStatus" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityFilerCategory" xlink:label="dei_EntityFilerCategory" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityRegistrantName" xlink:label="dei_EntityRegistrantName" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityVoluntaryFilers" xlink:label="dei_EntityVoluntaryFilers" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityWellKnownSeasonedIssuer" xlink:label="dei_EntityWellKnownSeasonedIssuer" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_TradingSymbol" xlink:label="dei_TradingSymbol" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="dei_DocumentInformationTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_DocumentInformationTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityRegistrantName" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityCentralIndexKey" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_TradingSymbol" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_CurrentFiscalYearEndDate" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityFilerCategory" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityCurrentReportingStatus" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityVoluntaryFilers" xlink:type="arc"/>
    <link:definitionArc order="8" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityWellKnownSeasonedIssuer" xlink:type="arc"/>
    <link:definitionArc order="9" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityCommonStockSharesOutstanding" xlink:type="arc"/>
    <link:definitionArc order="10" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_DocumentType" xlink:type="arc"/>
    <link:definitionArc order="11" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_DocumentPeriodEndDate" xlink:type="arc"/>
    <link:definitionArc order="12" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_DocumentFiscalYearFocus" xlink:type="arc"/>
    <link:definitionArc order="13" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_DocumentFiscalPeriodFocus" xlink:type="arc"/>
    <link:definitionArc order="14" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_AmendmentFlag" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-3-financial-condition-and-business-plan" xlink:href="clsn-20180331.xsd#statement-note-3-financial-condition-and-business-plan" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-3-financial-condition-and-business-plan" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SubstantialDoubtAboutGoingConcernTextBlock" xlink:label="us-gaap_SubstantialDoubtAboutGoingConcernTextBlock" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="us-gaap_SubstantialDoubtAboutGoingConcernTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-5-net-loss-per-common-share" xlink:href="clsn-20180331.xsd#statement-note-5-net-loss-per-common-share" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-5-net-loss-per-common-share" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_EarningsPerShareTextBlock" xlink:label="us-gaap_EarningsPerShareTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="us-gaap_EarningsPerShareTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-6-fair-value-of-financial-instruments" xlink:href="clsn-20180331.xsd#statement-note-6-fair-value-of-financial-instruments" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-6-fair-value-of-financial-instruments" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DerivativesAndFairValueTextBlock" xlink:label="us-gaap_DerivativesAndFairValueTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="us-gaap_DerivativesAndFairValueTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-7-fair-value-of-measurements" xlink:href="clsn-20180331.xsd#statement-note-7-fair-value-of-measurements" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-7-fair-value-of-measurements" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FairValueDisclosuresTextBlock" xlink:label="us-gaap_FairValueDisclosuresTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="us-gaap_FairValueDisclosuresTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-8-acquisition-of-egen-assets" xlink:href="clsn-20180331.xsd#statement-note-8-acquisition-of-egen-assets" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-8-acquisition-of-egen-assets" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_EGENIncMember" xlink:label="clsn_EGENIncMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_GlioblastomaMultiformeBrainCancerStudyMilestoneMember" xlink:label="clsn_GlioblastomaMultiformeBrainCancerStudyMilestoneMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_IndefiniteLivedInProcessResearchAndDevelopmentMember" xlink:label="clsn_IndefiniteLivedInProcessResearchAndDevelopmentMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_OvarianCancerStudyMilestoneMember" xlink:label="clsn_OvarianCancerStudyMilestoneMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationDisclosureTextBlock" xlink:label="us-gaap_BusinessCombinationDisclosureTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ContingentConsiderationByTypeAxis" xlink:label="us-gaap_ContingentConsiderationByTypeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ContingentConsiderationTypeDomain" xlink:label="us-gaap_ContingentConsiderationTypeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ContingentConsiderationTypeDomain" xlink:label="us-gaap_ContingentConsiderationTypeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:label="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NoncompeteAgreementsMember" xlink:label="us-gaap_NoncompeteAgreementsMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ContingentConsiderationByTypeAxis" xlink:to="us-gaap_ContingentConsiderationTypeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_BusinessAcquisitionAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="clsn_EGENIncMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="srt_RangeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember-default" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_ContingentConsiderationByTypeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="clsn_OvarianCancerStudyMilestoneMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_ContingentConsiderationByTypeAxis" xlink:to="us-gaap_ContingentConsiderationTypeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="clsn_GlioblastomaMultiformeBrainCancerStudyMilestoneMember" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="clsn_IndefiniteLivedInProcessResearchAndDevelopmentMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_NoncompeteAgreementsMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="us-gaap_BusinessCombinationDisclosureTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-10-note-payable" xlink:href="clsn-20180331.xsd#statement-note-10-note-payable" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-10-note-payable" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_EGENIncMember" xlink:label="clsn_EGENIncMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_FirstFiftyPercentMember" xlink:label="clsn_FirstFiftyPercentMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_HerculesCreditAgreementMember" xlink:label="clsn_HerculesCreditAgreementMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_HerculesMember" xlink:label="clsn_HerculesMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_HerculesWarrantMember" xlink:label="clsn_HerculesWarrantMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_SecondFiftyPercentMember" xlink:label="clsn_SecondFiftyPercentMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightAxis" xlink:label="us-gaap_ClassOfWarrantOrRightAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightDomain" xlink:label="us-gaap_ClassOfWarrantOrRightDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightDomain" xlink:label="us-gaap_ClassOfWarrantOrRightDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtDisclosureTextBlock" xlink:label="us-gaap_DebtDisclosureTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ScenarioUnspecifiedDomain" xlink:label="us-gaap_ScenarioUnspecifiedDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ScenarioUnspecifiedDomain" xlink:label="us-gaap_ScenarioUnspecifiedDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementScenarioAxis" xlink:label="us-gaap_StatementScenarioAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_StatementScenarioAxis" xlink:to="us-gaap_ScenarioUnspecifiedDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ClassOfWarrantOrRightAxis" xlink:to="us-gaap_ClassOfWarrantOrRightDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="srt_CounterpartyNameAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="clsn_HerculesMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_DebtInstrumentAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="clsn_HerculesCreditAgreementMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_BusinessAcquisitionAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="clsn_EGENIncMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_StatementScenarioAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ScenarioUnspecifiedDomain" xlink:to="clsn_FirstFiftyPercentMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_StatementScenarioAxis" xlink:to="us-gaap_ScenarioUnspecifiedDomain-default" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_ClassOfWarrantOrRightAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_HerculesWarrantMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_ClassOfWarrantOrRightAxis" xlink:to="us-gaap_ClassOfWarrantOrRightDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ScenarioUnspecifiedDomain" xlink:to="clsn_SecondFiftyPercentMember" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="us-gaap_DebtDisclosureTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-11-stockholders-equity" xlink:href="clsn-20180331.xsd#statement-note-11-stockholders-equity" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-11-stockholders-equity" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ATMAgreementMember" xlink:label="clsn_ATMAgreementMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_AdditionalWarrantsIssuedToUnderwriterMember" xlink:label="clsn_AdditionalWarrantsIssuedToUnderwriterMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_February142017PublicOfferingMember" xlink:label="clsn_February142017PublicOfferingMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_February2013PreferredStockOfferingMember" xlink:label="clsn_February2013PreferredStockOfferingMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_JanuaryTwoThousandFourteenCommonStockOfferingMember" xlink:label="clsn_JanuaryTwoThousandFourteenCommonStockOfferingMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_July2017DirectOfferingMember" xlink:label="clsn_July2017DirectOfferingMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_May2015CommonStockOfferingMember" xlink:label="clsn_May2015CommonStockOfferingMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_October2017UnderwrittenOfferingMember" xlink:label="clsn_October2017UnderwrittenOfferingMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_PreFundedSeriesBBWarrantMember" xlink:label="clsn_PreFundedSeriesBBWarrantMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_PreFundedSeriesCCCWarrantsMember" xlink:label="clsn_PreFundedSeriesCCCWarrantsMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ReverseStockSplitMember" xlink:label="clsn_ReverseStockSplitMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_SeriesAAAWarrantsMember" xlink:label="clsn_SeriesAAAWarrantsMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_SeriesAAWarrantMember" xlink:label="clsn_SeriesAAWarrantMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_SeriesBBBWarrantsMember" xlink:label="clsn_SeriesBBBWarrantsMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_SeriesDDDWarrantsMember" xlink:label="clsn_SeriesDDDWarrantsMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_TwoThousandFifteenWarrantsMember" xlink:label="clsn_TwoThousandFifteenWarrantsMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_TwoThousandThirteenWarrants2014WarrantsAndJune2016WarrantsMember" xlink:label="clsn_TwoThousandThirteenWarrants2014WarrantsAndJune2016WarrantsMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightAxis" xlink:label="us-gaap_ClassOfWarrantOrRightAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightDomain" xlink:label="us-gaap_ClassOfWarrantOrRightDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightDomain" xlink:label="us-gaap_ClassOfWarrantOrRightDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NonmonetaryTransactionTypeAxis" xlink:label="us-gaap_NonmonetaryTransactionTypeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NonmonetaryTransactionTypeDomain" xlink:label="us-gaap_NonmonetaryTransactionTypeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NonmonetaryTransactionTypeDomain" xlink:label="us-gaap_NonmonetaryTransactionTypeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StockholdersEquityNoteDisclosureTextBlock" xlink:label="us-gaap_StockholdersEquityNoteDisclosureTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:label="us-gaap_SubsidiarySaleOfStockAxis" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ClassOfWarrantOrRightAxis" xlink:to="us-gaap_ClassOfWarrantOrRightDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_NonmonetaryTransactionTypeAxis" xlink:to="us-gaap_NonmonetaryTransactionTypeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_NonmonetaryTransactionTypeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NonmonetaryTransactionTypeDomain" xlink:to="clsn_ReverseStockSplitMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_NonmonetaryTransactionTypeAxis" xlink:to="us-gaap_NonmonetaryTransactionTypeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_SubsidiarySaleOfStockAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_October2017UnderwrittenOfferingMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain-default" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_ClassOfWarrantOrRightAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_AdditionalWarrantsIssuedToUnderwriterMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_ClassOfWarrantOrRightAxis" xlink:to="us-gaap_ClassOfWarrantOrRightDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_July2017DirectOfferingMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_PreFundedSeriesCCCWarrantsMember" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_SeriesAAAWarrantsMember" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_SeriesBBBWarrantsMember" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_SeriesDDDWarrantsMember" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_February142017PublicOfferingMember" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_SeriesAAWarrantMember" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_PreFundedSeriesBBWarrantMember" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_February2013PreferredStockOfferingMember" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_JanuaryTwoThousandFourteenCommonStockOfferingMember" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_TwoThousandThirteenWarrants2014WarrantsAndJune2016WarrantsMember" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_May2015CommonStockOfferingMember" xlink:type="arc"/>
    <link:definitionArc order="8" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_TwoThousandFifteenWarrantsMember" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_ATMAgreementMember" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="us-gaap_StockholdersEquityNoteDisclosureTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-12-stockbased-compensation" xlink:href="clsn-20180331.xsd#statement-note-12-stockbased-compensation" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-12-stockbased-compensation" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_StockIncentivePlan2007Member" xlink:label="clsn_StockIncentivePlan2007Member" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureOfCompensationRelatedCostsShareBasedPaymentsTextBlock" xlink:label="us-gaap_DisclosureOfCompensationRelatedCostsShareBasedPaymentsTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="us-gaap_EmployeeStockOptionMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PlanNameAxis" xlink:label="us-gaap_PlanNameAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PlanNameDomain" xlink:label="us-gaap_PlanNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PlanNameDomain" xlink:label="us-gaap_PlanNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_PlanNameAxis" xlink:to="us-gaap_PlanNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_AwardTypeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_PlanNameAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PlanNameDomain" xlink:to="clsn_StockIncentivePlan2007Member" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_PlanNameAxis" xlink:to="us-gaap_PlanNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="srt_RangeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember-default" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="us-gaap_DisclosureOfCompensationRelatedCostsShareBasedPaymentsTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-13-earnout-milestone-liability" xlink:href="clsn-20180331.xsd#statement-note-13-earnout-milestone-liability" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-13-earnout-milestone-liability" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_EGENIncMember" xlink:label="clsn_EGENIncMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_EarnoutMilestoneLiabilityDisclosureTextBlock" xlink:label="clsn_EarnoutMilestoneLiabilityDisclosureTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_BusinessAcquisitionAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="clsn_EGENIncMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="srt_RangeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="clsn_EarnoutMilestoneLiabilityDisclosureTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-14-contingent-liabilities-and-commitments" xlink:href="clsn-20180331.xsd#statement-note-14-contingent-liabilities-and-commitments" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-14-contingent-liabilities-and-commitments" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_LawrencevilleNewJerseyMember" xlink:label="clsn_LawrencevilleNewJerseyMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_PremisesLocatedInHuntsvilleAlabamaMember" xlink:label="clsn_PremisesLocatedInHuntsvilleAlabamaMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CommitmentsAndContingenciesDisclosureTextBlock" xlink:label="us-gaap_CommitmentsAndContingenciesDisclosureTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CreditFacilityAxis" xlink:label="us-gaap_CreditFacilityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CreditFacilityDomain" xlink:label="us-gaap_CreditFacilityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CreditFacilityDomain" xlink:label="us-gaap_CreditFacilityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LeaseArrangementTypeAxis" xlink:label="us-gaap_LeaseArrangementTypeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LeaseArrangementTypeDomain" xlink:label="us-gaap_LeaseArrangementTypeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LeaseArrangementTypeDomain" xlink:label="us-gaap_LeaseArrangementTypeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StandbyLettersOfCreditMember" xlink:label="us-gaap_StandbyLettersOfCreditMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_CreditFacilityAxis" xlink:to="us-gaap_CreditFacilityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_LeaseArrangementTypeAxis" xlink:to="us-gaap_LeaseArrangementTypeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_LeaseArrangementTypeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LeaseArrangementTypeDomain" xlink:to="clsn_LawrencevilleNewJerseyMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_LeaseArrangementTypeAxis" xlink:to="us-gaap_LeaseArrangementTypeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_CreditFacilityAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CreditFacilityDomain" xlink:to="us-gaap_StandbyLettersOfCreditMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_CreditFacilityAxis" xlink:to="us-gaap_CreditFacilityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LeaseArrangementTypeDomain" xlink:to="clsn_PremisesLocatedInHuntsvilleAlabamaMember" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="us-gaap_CommitmentsAndContingenciesDisclosureTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-15-technology-development-and-licensing-agreements" xlink:href="clsn-20180331.xsd#statement-note-15-technology-development-and-licensing-agreements" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-15-technology-development-and-licensing-agreements" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_HisunMember" xlink:label="clsn_HisunMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_LicensingTransactionTextBlock" xlink:label="clsn_LicensingTransactionTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis" xlink:label="us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DisclosureTextBlockAbstract" xlink:label="us-gaap_DisclosureTextBlockAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LegalEntityTypeOfCounterpartyDomain" xlink:label="us-gaap_LegalEntityTypeOfCounterpartyDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LegalEntityTypeOfCounterpartyDomain" xlink:label="us-gaap_LegalEntityTypeOfCounterpartyDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DisclosureTextBlockAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis" xlink:to="us-gaap_LegalEntityTypeOfCounterpartyDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LegalEntityTypeOfCounterpartyDomain" xlink:to="clsn_HisunMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis" xlink:to="us-gaap_LegalEntityTypeOfCounterpartyDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisclosureTextBlockAbstract" xlink:to="clsn_LicensingTransactionTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-6-fair-value-of-financial-instruments-tables" xlink:href="clsn-20180331.xsd#statement-note-6-fair-value-of-financial-instruments-tables" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-6-fair-value-of-financial-instruments-tables" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ScheduleOfCostFairValueAndMaturitiesOfShorttermInvestmentsTableTextBlock" xlink:label="clsn_ScheduleOfCostFairValueAndMaturitiesOfShorttermInvestmentsTableTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_InvestmentIncomeTextBlock" xlink:label="us-gaap_InvestmentIncomeTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ScheduleOfUnrealizedLossOnInvestmentsTableTextBlock" xlink:label="us-gaap_ScheduleOfUnrealizedLossOnInvestmentsTableTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_TableTextBlock" xlink:label="us-gaap_TableTextBlock" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_TableTextBlock" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TableTextBlock" xlink:to="clsn_ScheduleOfCostFairValueAndMaturitiesOfShorttermInvestmentsTableTextBlock" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TableTextBlock" xlink:to="us-gaap_InvestmentIncomeTextBlock" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TableTextBlock" xlink:to="us-gaap_ScheduleOfUnrealizedLossOnInvestmentsTableTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-7-fair-value-of-measurements-tables" xlink:href="clsn-20180331.xsd#statement-note-7-fair-value-of-measurements-tables" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-7-fair-value-of-measurements-tables" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ScheduleOfFairValueAssetsAndLiabilitiesMeasuredOnRecurringBasisTableTextBlock" xlink:label="us-gaap_ScheduleOfFairValueAssetsAndLiabilitiesMeasuredOnRecurringBasisTableTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_TableTextBlock" xlink:label="us-gaap_TableTextBlock" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_TableTextBlock" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TableTextBlock" xlink:to="us-gaap_ScheduleOfFairValueAssetsAndLiabilitiesMeasuredOnRecurringBasisTableTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-8-acquisition-of-egen-assets-tables" xlink:href="clsn-20180331.xsd#statement-note-8-acquisition-of-egen-assets-tables" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-8-acquisition-of-egen-assets-tables" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ScheduleOfRecognizedIdentifiedAssetsAcquiredAndLiabilitiesAssumedTableTextBlock" xlink:label="us-gaap_ScheduleOfRecognizedIdentifiedAssetsAcquiredAndLiabilitiesAssumedTableTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_TableTextBlock" xlink:label="us-gaap_TableTextBlock" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_TableTextBlock" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TableTextBlock" xlink:to="us-gaap_ScheduleOfRecognizedIdentifiedAssetsAcquiredAndLiabilitiesAssumedTableTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-9-accrued-liabilities-tables" xlink:href="clsn-20180331.xsd#statement-note-9-accrued-liabilities-tables" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-9-accrued-liabilities-tables" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ScheduleOfAccruedLiabilitiesTableTextBlock" xlink:label="us-gaap_ScheduleOfAccruedLiabilitiesTableTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_TableTextBlock" xlink:label="us-gaap_TableTextBlock" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_TableTextBlock" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TableTextBlock" xlink:to="us-gaap_ScheduleOfAccruedLiabilitiesTableTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-12-stockbased-compensation-tables" xlink:href="clsn-20180331.xsd#statement-note-12-stockbased-compensation-tables" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-12-stockbased-compensation-tables" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ScheduleOfSharebasedCompensationStockOptionsAndRestrictedStockAwardsActivityTableTextBlock" xlink:label="clsn_ScheduleOfSharebasedCompensationStockOptionsAndRestrictedStockAwardsActivityTableTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:label="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_TableTextBlock" xlink:label="us-gaap_TableTextBlock" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_TableTextBlock" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TableTextBlock" xlink:to="clsn_ScheduleOfSharebasedCompensationStockOptionsAndRestrictedStockAwardsActivityTableTextBlock" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TableTextBlock" xlink:to="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-13-earnout-milestone-liability-tables" xlink:href="clsn-20180331.xsd#statement-note-13-earnout-milestone-liability-tables" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-13-earnout-milestone-liability-tables" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ScheduleOfChangesInEarnOutMilestoneLiabilitiesTableTextBlock" xlink:label="clsn_ScheduleOfChangesInEarnOutMilestoneLiabilitiesTableTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ScheduleOfMilestoneRiskAdjustmentAssessmentTableTextBlock" xlink:label="clsn_ScheduleOfMilestoneRiskAdjustmentAssessmentTableTextBlock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_TableTextBlock" xlink:label="us-gaap_TableTextBlock" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_TableTextBlock" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TableTextBlock" xlink:to="clsn_ScheduleOfChangesInEarnOutMilestoneLiabilitiesTableTextBlock" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TableTextBlock" xlink:to="clsn_ScheduleOfMilestoneRiskAdjustmentAssessmentTableTextBlock" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-3-financial-condition-and-business-plan-details-textual" xlink:href="clsn-20180331.xsd#statement-note-3-financial-condition-and-business-plan-details-textual" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-3-financial-condition-and-business-plan-details-textual" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_AggregateOfferingPriceAdditions" xlink:label="clsn_AggregateOfferingPriceAdditions" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_CashInvestmentSecuritiesAndInterestReceivable" xlink:label="clsn_CashInvestmentSecuritiesAndInterestReceivable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_CashInvestmentSecuritiesAndInterestReceivable" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_AggregateOfferingPriceAdditions" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-5-net-loss-per-common-share-details-textual" xlink:href="clsn-20180331.xsd#statement-note-5-net-loss-per-common-share-details-textual" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-5-net-loss-per-common-share-details-textual" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_NumberOfSharesOfCommonStockIssuableUponExerciseOfWarrantsAndEquityAwards" xlink:label="clsn_NumberOfSharesOfCommonStockIssuableUponExerciseOfWarrantsAndEquityAwards" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_NumberOfSharesOfCommonStockIssuableUponExerciseOfWarrantsAndEquityAwards" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-6-fair-value-of-financial-instruments-details-textual" xlink:href="clsn-20180331.xsd#statement-note-6-fair-value-of-financial-instruments-details-textual" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-6-fair-value-of-financial-instruments-details-textual" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-7-fair-value-of-measurements-details-textual" xlink:href="clsn-20180331.xsd#statement-note-7-fair-value-of-measurements-details-textual" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-7-fair-value-of-measurements-details-textual" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FairValueAssetsLevel1ToLevel2TransfersAmount" xlink:label="us-gaap_FairValueAssetsLevel1ToLevel2TransfersAmount" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FairValueNetDerivativeAssetLiabilityMeasuredOnRecurringBasisUnobservableInputsReconciliationTransfersIntoLevel3" xlink:label="us-gaap_FairValueNetDerivativeAssetLiabilityMeasuredOnRecurringBasisUnobservableInputsReconciliationTransfersIntoLevel3" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_FairValueAssetsLevel1ToLevel2TransfersAmount" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_FairValueNetDerivativeAssetLiabilityMeasuredOnRecurringBasisUnobservableInputsReconciliationTransfersIntoLevel3" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-8-acquisition-of-egen-assets-details-textual" xlink:href="clsn-20180331.xsd#statement-note-8-acquisition-of-egen-assets-details-textual" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-8-acquisition-of-egen-assets-details-textual" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_EGENIncMember" xlink:label="clsn_EGENIncMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_GlioblastomaMultiformeBrainCancerStudyMilestoneMember" xlink:label="clsn_GlioblastomaMultiformeBrainCancerStudyMilestoneMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_IndefiniteLivedInProcessResearchAndDevelopmentMember" xlink:label="clsn_IndefiniteLivedInProcessResearchAndDevelopmentMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_OvarianCancerStudyMilestoneMember" xlink:label="clsn_OvarianCancerStudyMilestoneMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AmortizationOfIntangibleAssets" xlink:label="us-gaap_AmortizationOfIntangibleAssets" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AssetImpairmentCharges" xlink:label="us-gaap_AssetImpairmentCharges" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionEquityInterestsIssuedOrIssuableNumberOfSharesIssued" xlink:label="us-gaap_BusinessAcquisitionEquityInterestsIssuedOrIssuableNumberOfSharesIssued" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationConsiderationTransferred1" xlink:label="us-gaap_BusinessCombinationConsiderationTransferred1" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh" xlink:label="us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ContingentConsiderationByTypeAxis" xlink:label="us-gaap_ContingentConsiderationByTypeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ContingentConsiderationTypeDomain" xlink:label="us-gaap_ContingentConsiderationTypeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ContingentConsiderationTypeDomain" xlink:label="us-gaap_ContingentConsiderationTypeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife" xlink:label="us-gaap_FiniteLivedIntangibleAssetUsefulLife" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:label="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FinitelivedIntangibleAssetsAcquired1" xlink:label="us-gaap_FinitelivedIntangibleAssetsAcquired1" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_GoodwillAcquiredDuringPeriod" xlink:label="us-gaap_GoodwillAcquiredDuringPeriod" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill" xlink:label="us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IndefinitelivedIntangibleAssetsAcquired" xlink:label="us-gaap_IndefinitelivedIntangibleAssetsAcquired" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NoncompeteAgreementsMember" xlink:label="us-gaap_NoncompeteAgreementsMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PaymentsToAcquireBusinessesGross" xlink:label="us-gaap_PaymentsToAcquireBusinessesGross" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesAcquisitions" xlink:label="us-gaap_StockIssuedDuringPeriodSharesAcquisitions" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ContingentConsiderationByTypeAxis" xlink:to="us-gaap_ContingentConsiderationTypeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_BusinessAcquisitionAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="clsn_EGENIncMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="srt_RangeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember-default" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_ContingentConsiderationByTypeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="clsn_OvarianCancerStudyMilestoneMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_ContingentConsiderationByTypeAxis" xlink:to="us-gaap_ContingentConsiderationTypeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="clsn_GlioblastomaMultiformeBrainCancerStudyMilestoneMember" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="clsn_IndefiniteLivedInProcessResearchAndDevelopmentMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_NoncompeteAgreementsMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessCombinationConsiderationTransferred1" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_PaymentsToAcquireBusinessesGross" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesAcquisitions" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessAcquisitionEquityInterestsIssuedOrIssuableNumberOfSharesIssued" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_IndefinitelivedIntangibleAssetsAcquired" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AssetImpairmentCharges" xlink:type="arc"/>
    <link:definitionArc order="8" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill" xlink:type="arc"/>
    <link:definitionArc order="9" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetUsefulLife" xlink:type="arc"/>
    <link:definitionArc order="10" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_FinitelivedIntangibleAssetsAcquired1" xlink:type="arc"/>
    <link:definitionArc order="11" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AmortizationOfIntangibleAssets" xlink:type="arc"/>
    <link:definitionArc order="12" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:type="arc"/>
    <link:definitionArc order="13" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" xlink:type="arc"/>
    <link:definitionArc order="14" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_GoodwillAcquiredDuringPeriod" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-10-note-payable-details-textual" xlink:href="clsn-20180331.xsd#statement-note-10-note-payable-details-textual" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-10-note-payable-details-textual" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_AmortizationPeriodForPrincipalAndInterest" xlink:label="clsn_AmortizationPeriodForPrincipalAndInterest" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_EGENIncMember" xlink:label="clsn_EGENIncMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_FirstFiftyPercentMember" xlink:label="clsn_FirstFiftyPercentMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_HerculesCreditAgreementMember" xlink:label="clsn_HerculesCreditAgreementMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_HerculesMember" xlink:label="clsn_HerculesMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_HerculesWarrantMember" xlink:label="clsn_HerculesWarrantMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_LineOfCreditFacilityOriginalLoanFeePercent" xlink:label="clsn_LineOfCreditFacilityOriginalLoanFeePercent" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_SecondFiftyPercentMember" xlink:label="clsn_SecondFiftyPercentMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AmortizationOfFinancingCosts" xlink:label="us-gaap_AmortizationOfFinancingCosts" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightAxis" xlink:label="us-gaap_ClassOfWarrantOrRightAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightDomain" xlink:label="us-gaap_ClassOfWarrantOrRightDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightDomain" xlink:label="us-gaap_ClassOfWarrantOrRightDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1" xlink:label="us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight" xlink:label="us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtInstrumentBasisSpreadOnVariableRate1" xlink:label="us-gaap_DebtInstrumentBasisSpreadOnVariableRate1" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtInstrumentUnamortizedDiscount" xlink:label="us-gaap_DebtInstrumentUnamortizedDiscount" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DeferredFinanceCostsGross" xlink:label="us-gaap_DeferredFinanceCostsGross" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DeferredFinanceCostsNet" xlink:label="us-gaap_DeferredFinanceCostsNet" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_InterestExpenseDebt" xlink:label="us-gaap_InterestExpenseDebt" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity" xlink:label="us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PaymentsToAcquireBusinessesGross" xlink:label="us-gaap_PaymentsToAcquireBusinessesGross" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ProceedsFromLinesOfCredit" xlink:label="us-gaap_ProceedsFromLinesOfCredit" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_RepaymentsOfLinesOfCredit" xlink:label="us-gaap_RepaymentsOfLinesOfCredit" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ScenarioUnspecifiedDomain" xlink:label="us-gaap_ScenarioUnspecifiedDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ScenarioUnspecifiedDomain" xlink:label="us-gaap_ScenarioUnspecifiedDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementScenarioAxis" xlink:label="us-gaap_StatementScenarioAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_StatementScenarioAxis" xlink:to="us-gaap_ScenarioUnspecifiedDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ClassOfWarrantOrRightAxis" xlink:to="us-gaap_ClassOfWarrantOrRightDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="srt_CounterpartyNameAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="clsn_HerculesMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_DebtInstrumentAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="clsn_HerculesCreditAgreementMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_BusinessAcquisitionAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="clsn_EGENIncMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_StatementScenarioAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ScenarioUnspecifiedDomain" xlink:to="clsn_FirstFiftyPercentMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_StatementScenarioAxis" xlink:to="us-gaap_ScenarioUnspecifiedDomain-default" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_ClassOfWarrantOrRightAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_HerculesWarrantMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_ClassOfWarrantOrRightAxis" xlink:to="us-gaap_ClassOfWarrantOrRightDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ScenarioUnspecifiedDomain" xlink:to="clsn_SecondFiftyPercentMember" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ProceedsFromLinesOfCredit" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_RepaymentsOfLinesOfCredit" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_PaymentsToAcquireBusinessesGross" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentBasisSpreadOnVariableRate1" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_AmortizationPeriodForPrincipalAndInterest" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DeferredFinanceCostsNet" xlink:type="arc"/>
    <link:definitionArc order="8" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtInstrumentUnamortizedDiscount" xlink:type="arc"/>
    <link:definitionArc order="9" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight" xlink:type="arc"/>
    <link:definitionArc order="10" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1" xlink:type="arc"/>
    <link:definitionArc order="11" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_LineOfCreditFacilityOriginalLoanFeePercent" xlink:type="arc"/>
    <link:definitionArc order="12" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DeferredFinanceCostsGross" xlink:type="arc"/>
    <link:definitionArc order="13" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_InterestExpenseDebt" xlink:type="arc"/>
    <link:definitionArc order="14" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AmortizationOfFinancingCosts" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-11-stockholders-equity-details-textual" xlink:href="clsn-20180331.xsd#statement-note-11-stockholders-equity-details-textual" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-11-stockholders-equity-details-textual" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ATMAgreementMember" xlink:label="clsn_ATMAgreementMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_AdditionalWarrantsIssuedToUnderwriterMember" xlink:label="clsn_AdditionalWarrantsIssuedToUnderwriterMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_AggregateOfCommonAndPreferredStockSharesAuthorized" xlink:label="clsn_AggregateOfCommonAndPreferredStockSharesAuthorized" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_AggregateOfferingPrice" xlink:label="clsn_AggregateOfferingPrice" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_AggregateOfferingPriceAdditions" xlink:label="clsn_AggregateOfferingPriceAdditions" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_AggregateOfferingPriceRemainingAmount" xlink:label="clsn_AggregateOfferingPriceRemainingAmount" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_BeneficialOwnershipPercentageThreshold" xlink:label="clsn_BeneficialOwnershipPercentageThreshold" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ClassOfWarrantOrRightExercisablePeriod" xlink:label="clsn_ClassOfWarrantOrRightExercisablePeriod" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ClassOfWarrantOrRightExercisedDuringPeriod" xlink:label="clsn_ClassOfWarrantOrRightExercisedDuringPeriod" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ClassOfWarrantOrRightNumberOfWarrantsIssuedWithStock" xlink:label="clsn_ClassOfWarrantOrRightNumberOfWarrantsIssuedWithStock" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ClassOfWarrantOrRightOfferedPriceOfWarrantsOrRights" xlink:label="clsn_ClassOfWarrantOrRightOfferedPriceOfWarrantsOrRights" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ClassOfWarrantOrRightTerm" xlink:label="clsn_ClassOfWarrantOrRightTerm" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ClassOfWarrantOrRightWeightedAverageRemainingContractualTerm" xlink:label="clsn_ClassOfWarrantOrRightWeightedAverageRemainingContractualTerm" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_CommissionOnProceedsFromAtmSharesPercent" xlink:label="clsn_CommissionOnProceedsFromAtmSharesPercent" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_February142017PublicOfferingMember" xlink:label="clsn_February142017PublicOfferingMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_February2013PreferredStockOfferingMember" xlink:label="clsn_February2013PreferredStockOfferingMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_IncreaseDecreaseInFairValueOfWarrants" xlink:label="clsn_IncreaseDecreaseInFairValueOfWarrants" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_JanuaryTwoThousandFourteenCommonStockOfferingMember" xlink:label="clsn_JanuaryTwoThousandFourteenCommonStockOfferingMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_July2017DirectOfferingMember" xlink:label="clsn_July2017DirectOfferingMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_MaximumBeneficialOwnershipOfThePurchaser" xlink:label="clsn_MaximumBeneficialOwnershipOfThePurchaser" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_May2015CommonStockOfferingMember" xlink:label="clsn_May2015CommonStockOfferingMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_October2017UnderwrittenOfferingMember" xlink:label="clsn_October2017UnderwrittenOfferingMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_PreFundedSeriesBBWarrantMember" xlink:label="clsn_PreFundedSeriesBBWarrantMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_PreFundedSeriesCCCWarrantsMember" xlink:label="clsn_PreFundedSeriesCCCWarrantsMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ProceedsFromIssuanceOfCommonStockAndWarrants" xlink:label="clsn_ProceedsFromIssuanceOfCommonStockAndWarrants" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ProceedsFromIssuanceOfCommonStockGross" xlink:label="clsn_ProceedsFromIssuanceOfCommonStockGross" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ReverseStockSplitMember" xlink:label="clsn_ReverseStockSplitMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_SeriesAAAWarrantsMember" xlink:label="clsn_SeriesAAAWarrantsMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_SeriesAAWarrantMember" xlink:label="clsn_SeriesAAWarrantMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_SeriesBBBWarrantsMember" xlink:label="clsn_SeriesBBBWarrantsMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_SeriesDDDWarrantsMember" xlink:label="clsn_SeriesDDDWarrantsMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ShelfRegistrationStatementAmount" xlink:label="clsn_ShelfRegistrationStatementAmount" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_StockIssuedDuringPeriodSharesExerciseOfWarrants" xlink:label="clsn_StockIssuedDuringPeriodSharesExerciseOfWarrants" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_TwoThousandFifteenWarrantsMember" xlink:label="clsn_TwoThousandFifteenWarrantsMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_TwoThousandThirteenWarrants2014WarrantsAndJune2016WarrantsMember" xlink:label="clsn_TwoThousandThirteenWarrants2014WarrantsAndJune2016WarrantsMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_WarrantsIssuedExpirationPeriod" xlink:label="clsn_WarrantsIssuedExpirationPeriod" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightAxis" xlink:label="us-gaap_ClassOfWarrantOrRightAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightDomain" xlink:label="us-gaap_ClassOfWarrantOrRightDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightDomain" xlink:label="us-gaap_ClassOfWarrantOrRightDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1" xlink:label="us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight" xlink:label="us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights" xlink:label="us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ClassOfWarrantOrRightOutstanding" xlink:label="us-gaap_ClassOfWarrantOrRightOutstanding" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CommonStockParOrStatedValuePerShare" xlink:label="us-gaap_CommonStockParOrStatedValuePerShare" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CommonStockSharesAuthorized" xlink:label="us-gaap_CommonStockSharesAuthorized" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CommonStockSharesOutstanding" xlink:label="us-gaap_CommonStockSharesOutstanding" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LegalFees" xlink:label="us-gaap_LegalFees" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NonmonetaryTransactionTypeAxis" xlink:label="us-gaap_NonmonetaryTransactionTypeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NonmonetaryTransactionTypeDomain" xlink:label="us-gaap_NonmonetaryTransactionTypeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NonmonetaryTransactionTypeDomain" xlink:label="us-gaap_NonmonetaryTransactionTypeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PreferredStockSharesAuthorized" xlink:label="us-gaap_PreferredStockSharesAuthorized" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:label="us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ProceedsFromIssuanceOfWarrants" xlink:label="us-gaap_ProceedsFromIssuanceOfWarrants" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ProceedsFromWarrantExercises" xlink:label="us-gaap_ProceedsFromWarrantExercises" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SharePrice" xlink:label="us-gaap_SharePrice" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SharesIssuedPricePerShare" xlink:label="us-gaap_SharesIssuedPricePerShare" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StockholdersEquityNoteStockSplitConversionRatio1" xlink:label="us-gaap_StockholdersEquityNoteStockSplitConversionRatio1" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:label="us-gaap_SubsidiarySaleOfStockAxis" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ClassOfWarrantOrRightAxis" xlink:to="us-gaap_ClassOfWarrantOrRightDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_NonmonetaryTransactionTypeAxis" xlink:to="us-gaap_NonmonetaryTransactionTypeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_NonmonetaryTransactionTypeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NonmonetaryTransactionTypeDomain" xlink:to="clsn_ReverseStockSplitMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_NonmonetaryTransactionTypeAxis" xlink:to="us-gaap_NonmonetaryTransactionTypeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_SubsidiarySaleOfStockAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_October2017UnderwrittenOfferingMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain-default" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_ClassOfWarrantOrRightAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_AdditionalWarrantsIssuedToUnderwriterMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_ClassOfWarrantOrRightAxis" xlink:to="us-gaap_ClassOfWarrantOrRightDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_July2017DirectOfferingMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_PreFundedSeriesCCCWarrantsMember" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_SeriesAAAWarrantsMember" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_SeriesBBBWarrantsMember" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_SeriesDDDWarrantsMember" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_February142017PublicOfferingMember" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_SeriesAAWarrantMember" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_PreFundedSeriesBBWarrantMember" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_February2013PreferredStockOfferingMember" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_JanuaryTwoThousandFourteenCommonStockOfferingMember" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_TwoThousandThirteenWarrants2014WarrantsAndJune2016WarrantsMember" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_May2015CommonStockOfferingMember" xlink:type="arc"/>
    <link:definitionArc order="8" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ClassOfWarrantOrRightDomain" xlink:to="clsn_TwoThousandFifteenWarrantsMember" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="clsn_ATMAgreementMember" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_ShelfRegistrationStatementAmount" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CommonStockSharesAuthorized" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_PreferredStockSharesAuthorized" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_AggregateOfCommonAndPreferredStockSharesAuthorized" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockholdersEquityNoteStockSplitConversionRatio1" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CommonStockSharesOutstanding" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:type="arc"/>
    <link:definitionArc order="8" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ClassOfWarrantOrRightOutstanding" xlink:type="arc"/>
    <link:definitionArc order="9" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:type="arc"/>
    <link:definitionArc order="10" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CommonStockParOrStatedValuePerShare" xlink:type="arc"/>
    <link:definitionArc order="11" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights" xlink:type="arc"/>
    <link:definitionArc order="12" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_ClassOfWarrantOrRightNumberOfWarrantsIssuedWithStock" xlink:type="arc"/>
    <link:definitionArc order="13" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight" xlink:type="arc"/>
    <link:definitionArc order="14" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_ClassOfWarrantOrRightOfferedPriceOfWarrantsOrRights" xlink:type="arc"/>
    <link:definitionArc order="15" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_SharesIssuedPricePerShare" xlink:type="arc"/>
    <link:definitionArc order="16" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_ClassOfWarrantOrRightExercisablePeriod" xlink:type="arc"/>
    <link:definitionArc order="17" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1" xlink:type="arc"/>
    <link:definitionArc order="18" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_WarrantsIssuedExpirationPeriod" xlink:type="arc"/>
    <link:definitionArc order="19" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_ProceedsFromIssuanceOfCommonStockAndWarrants" xlink:type="arc"/>
    <link:definitionArc order="20" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_SharePrice" xlink:type="arc"/>
    <link:definitionArc order="21" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_ProceedsFromIssuanceOfCommonStockGross" xlink:type="arc"/>
    <link:definitionArc order="22" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_BeneficialOwnershipPercentageThreshold" xlink:type="arc"/>
    <link:definitionArc order="23" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ProceedsFromIssuanceOfWarrants" xlink:type="arc"/>
    <link:definitionArc order="24" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_ClassOfWarrantOrRightExercisedDuringPeriod" xlink:type="arc"/>
    <link:definitionArc order="25" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_ClassOfWarrantOrRightTerm" xlink:type="arc"/>
    <link:definitionArc order="26" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_MaximumBeneficialOwnershipOfThePurchaser" xlink:type="arc"/>
    <link:definitionArc order="27" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:type="arc"/>
    <link:definitionArc order="28" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_StockIssuedDuringPeriodSharesExerciseOfWarrants" xlink:type="arc"/>
    <link:definitionArc order="29" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ProceedsFromWarrantExercises" xlink:type="arc"/>
    <link:definitionArc order="30" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_IncreaseDecreaseInFairValueOfWarrants" xlink:type="arc"/>
    <link:definitionArc order="31" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_ClassOfWarrantOrRightWeightedAverageRemainingContractualTerm" xlink:type="arc"/>
    <link:definitionArc order="32" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_AggregateOfferingPrice" xlink:type="arc"/>
    <link:definitionArc order="33" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_CommissionOnProceedsFromAtmSharesPercent" xlink:type="arc"/>
    <link:definitionArc order="34" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_LegalFees" xlink:type="arc"/>
    <link:definitionArc order="35" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_AggregateOfferingPriceAdditions" xlink:type="arc"/>
    <link:definitionArc order="36" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_AggregateOfferingPriceRemainingAmount" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-12-stockbased-compensation-details-textual" xlink:href="clsn-20180331.xsd#statement-note-12-stockbased-compensation-details-textual" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-12-stockbased-compensation-details-textual" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_PercentageOfFairMarketValueOfShares" xlink:label="clsn_PercentageOfFairMarketValueOfShares" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_PercentageOfOutstandingStockDeterminingFactorForIncentiveStockPrice" xlink:label="clsn_PercentageOfOutstandingStockDeterminingFactorForIncentiveStockPrice" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_StockIncentivePlan2007Member" xlink:label="clsn_StockIncentivePlan2007Member" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="us-gaap_EmployeeStockOptionMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PlanNameAxis" xlink:label="us-gaap_PlanNameAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PlanNameDomain" xlink:label="us-gaap_PlanNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PlanNameDomain" xlink:label="us-gaap_PlanNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_PlanNameAxis" xlink:to="us-gaap_PlanNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_AwardTypeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_PlanNameAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PlanNameDomain" xlink:to="clsn_StockIncentivePlan2007Member" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_PlanNameAxis" xlink:to="us-gaap_PlanNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="srt_RangeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember-default" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_PercentageOfFairMarketValueOfShares" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_PercentageOfOutstandingStockDeterminingFactorForIncentiveStockPrice" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" xlink:type="arc"/>
    <link:definitionArc order="8" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense" xlink:type="arc"/>
    <link:definitionArc order="9" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized" xlink:type="arc"/>
    <link:definitionArc order="10" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:type="arc"/>
    <link:definitionArc order="11" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-13-earnout-milestone-liability-details-textual" xlink:href="clsn-20180331.xsd#statement-note-13-earnout-milestone-liability-details-textual" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-13-earnout-milestone-liability-details-textual" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_EGENIncMember" xlink:label="clsn_EGENIncMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_EstimatedTimeToAchieveTheMilestone" xlink:label="clsn_EstimatedTimeToAchieveTheMilestone" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_GainLossFromChangeInFairValueOfEarnOutMilestoneLiability" xlink:label="clsn_GainLossFromChangeInFairValueOfEarnOutMilestoneLiability" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_RiskAdjustedAssessmentOfEachMilestone" xlink:label="clsn_RiskAdjustedAssessmentOfEachMilestone" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationConsiderationTransferredLiabilitiesIncurred" xlink:label="us-gaap_BusinessCombinationConsiderationTransferredLiabilitiesIncurred" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh" xlink:label="us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_BusinessAcquisitionAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="clsn_EGENIncMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="srt_RangeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessCombinationConsiderationTransferredLiabilitiesIncurred" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_RiskAdjustedAssessmentOfEachMilestone" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_EstimatedTimeToAchieveTheMilestone" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_GainLossFromChangeInFairValueOfEarnOutMilestoneLiability" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-14-contingent-liabilities-and-commitments-details-textual" xlink:href="clsn-20180331.xsd#statement-note-14-contingent-liabilities-and-commitments-details-textual" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-14-contingent-liabilities-and-commitments-details-textual" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ContractualObligationReductionNineteenMonthsFromInitialTerm" xlink:label="clsn_ContractualObligationReductionNineteenMonthsFromInitialTerm" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_ContractualObligationRemaining" xlink:label="clsn_ContractualObligationRemaining" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_LawrencevilleNewJerseyMember" xlink:label="clsn_LawrencevilleNewJerseyMember" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_NumberOfMonthsInWhichFreeRentIsProvided" xlink:label="clsn_NumberOfMonthsInWhichFreeRentIsProvided" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_OperatingLeasesMonthlyRentPayment" xlink:label="clsn_OperatingLeasesMonthlyRentPayment" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_OperatingLeasesMonthlyRentPaymentInFinalYear" xlink:label="clsn_OperatingLeasesMonthlyRentPaymentInFinalYear" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_OperatingLeasesMonthlyRentPaymentInFirstYear" xlink:label="clsn_OperatingLeasesMonthlyRentPaymentInFirstYear" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_PremisesLocatedInHuntsvilleAlabamaMember" xlink:label="clsn_PremisesLocatedInHuntsvilleAlabamaMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AreaOfRealEstateProperty" xlink:label="us-gaap_AreaOfRealEstateProperty" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ContractualObligation" xlink:label="us-gaap_ContractualObligation" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CreditFacilityAxis" xlink:label="us-gaap_CreditFacilityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CreditFacilityDomain" xlink:label="us-gaap_CreditFacilityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CreditFacilityDomain" xlink:label="us-gaap_CreditFacilityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LeaseArrangementTypeAxis" xlink:label="us-gaap_LeaseArrangementTypeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LeaseArrangementTypeDomain" xlink:label="us-gaap_LeaseArrangementTypeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LeaseArrangementTypeDomain" xlink:label="us-gaap_LeaseArrangementTypeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LesseeOperatingLeaseTermOfContract" xlink:label="us-gaap_LesseeOperatingLeaseTermOfContract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PaymentsForRent" xlink:label="us-gaap_PaymentsForRent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StandbyLettersOfCreditMember" xlink:label="us-gaap_StandbyLettersOfCreditMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_CreditFacilityAxis" xlink:to="us-gaap_CreditFacilityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_LeaseArrangementTypeAxis" xlink:to="us-gaap_LeaseArrangementTypeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_LeaseArrangementTypeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LeaseArrangementTypeDomain" xlink:to="clsn_LawrencevilleNewJerseyMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_LeaseArrangementTypeAxis" xlink:to="us-gaap_LeaseArrangementTypeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_CreditFacilityAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CreditFacilityDomain" xlink:to="us-gaap_StandbyLettersOfCreditMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_CreditFacilityAxis" xlink:to="us-gaap_CreditFacilityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LeaseArrangementTypeDomain" xlink:to="clsn_PremisesLocatedInHuntsvilleAlabamaMember" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AreaOfRealEstateProperty" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_LesseeOperatingLeaseTermOfContract" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_NumberOfMonthsInWhichFreeRentIsProvided" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_PaymentsForRent" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ContractualObligation" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_ContractualObligationReductionNineteenMonthsFromInitialTerm" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_ContractualObligationRemaining" xlink:type="arc"/>
    <link:definitionArc order="8" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_OperatingLeasesMonthlyRentPaymentInFirstYear" xlink:type="arc"/>
    <link:definitionArc order="9" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_OperatingLeasesMonthlyRentPaymentInFinalYear" xlink:type="arc"/>
    <link:definitionArc order="10" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_OperatingLeasesMonthlyRentPayment" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-15-technology-development-and-licensing-agreements-details-textual" xlink:href="clsn-20180331.xsd#statement-note-15-technology-development-and-licensing-agreements-details-textual" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-15-technology-development-and-licensing-agreements-details-textual" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_DeferredRevenueAmortizationPeriod" xlink:label="clsn_DeferredRevenueAmortizationPeriod" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_HisunMember" xlink:label="clsn_HisunMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis" xlink:label="us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DeferredRevenue" xlink:label="us-gaap_DeferredRevenue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LegalEntityTypeOfCounterpartyDomain" xlink:label="us-gaap_LegalEntityTypeOfCounterpartyDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LegalEntityTypeOfCounterpartyDomain" xlink:label="us-gaap_LegalEntityTypeOfCounterpartyDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ProceedsFromLicenseFeesReceived" xlink:label="us-gaap_ProceedsFromLicenseFeesReceived" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis" xlink:to="us-gaap_LegalEntityTypeOfCounterpartyDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LegalEntityTypeOfCounterpartyDomain" xlink:to="clsn_HisunMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis" xlink:to="us-gaap_LegalEntityTypeOfCounterpartyDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ProceedsFromLicenseFeesReceived" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DeferredRevenue" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_DeferredRevenueAmortizationPeriod" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-condensed-consolidated-balance-sheets-current-period-unaudited-parentheticals" xlink:href="clsn-20180331.xsd#statement-condensed-consolidated-balance-sheets-current-period-unaudited-parentheticals" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-condensed-consolidated-balance-sheets-current-period-unaudited-parentheticals" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" xlink:label="us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CommonStockParOrStatedValuePerShare" xlink:label="us-gaap_CommonStockParOrStatedValuePerShare" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CommonStockSharesAuthorized" xlink:label="us-gaap_CommonStockSharesAuthorized" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CommonStockSharesIssued" xlink:label="us-gaap_CommonStockSharesIssued" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CommonStockSharesOutstanding" xlink:label="us-gaap_CommonStockSharesOutstanding" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PreferredStockParOrStatedValuePerShare" xlink:label="us-gaap_PreferredStockParOrStatedValuePerShare" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PreferredStockSharesAuthorized" xlink:label="us-gaap_PreferredStockSharesAuthorized" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PreferredStockSharesIssued" xlink:label="us-gaap_PreferredStockSharesIssued" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PreferredStockSharesOutstanding" xlink:label="us-gaap_PreferredStockSharesOutstanding" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_TreasuryStockShares" xlink:label="us-gaap_TreasuryStockShares" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_PreferredStockParOrStatedValuePerShare" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_PreferredStockSharesAuthorized" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_PreferredStockSharesIssued" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_PreferredStockSharesOutstanding" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CommonStockParOrStatedValuePerShare" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CommonStockSharesAuthorized" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CommonStockSharesIssued" xlink:type="arc"/>
    <link:definitionArc order="8" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CommonStockSharesOutstanding" xlink:type="arc"/>
    <link:definitionArc order="9" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" xlink:type="arc"/>
    <link:definitionArc order="10" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_TreasuryStockShares" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-8-acquisition-of-egen-assets-fair-values-of-acquired-assets-and-liabilities-details" xlink:href="clsn-20180331.xsd#statement-note-8-acquisition-of-egen-assets-fair-values-of-acquired-assets-and-liabilities-details" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-8-acquisition-of-egen-assets-fair-values-of-acquired-assets-and-liabilities-details" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_EGENIncMember" xlink:label="clsn_EGENIncMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibles" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibles" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedNet" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedNet" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedPropertyPlantAndEquipment" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedPropertyPlantAndEquipment" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_Goodwill" xlink:label="us-gaap_Goodwill" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_BusinessAcquisitionAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="clsn_EGENIncMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedPropertyPlantAndEquipment" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibles" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_Goodwill" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedNet" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-13-earnout-milestone-liability-summary-of-the-changes-in-the-earnout-milestone-liability-details" xlink:href="clsn-20180331.xsd#statement-note-13-earnout-milestone-liability-summary-of-the-changes-in-the-earnout-milestone-liability-details" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-13-earnout-milestone-liability-summary-of-the-changes-in-the-earnout-milestone-liability-details" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_EarnoutMilestoneLiability" xlink:label="clsn_EarnoutMilestoneLiability" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_GainLossFromChangeInFairValueOfEarnOutMilestoneLiability" xlink:label="clsn_GainLossFromChangeInFairValueOfEarnOutMilestoneLiability" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_EarnoutMilestoneLiability" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_GainLossFromChangeInFairValueOfEarnOutMilestoneLiability" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-condensed-consolidated-statements-of-cash-flows-unaudited" xlink:href="clsn-20180331.xsd#statement-condensed-consolidated-statements-of-cash-flows-unaudited" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-condensed-consolidated-statements-of-cash-flows-unaudited" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_DeferredFinanceCharges" xlink:label="clsn_DeferredFinanceCharges" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AdjustmentsNoncashItemsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="us-gaap_AdjustmentsNoncashItemsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CashAndCashEquivalentsPeriodIncreaseDecrease" xlink:label="us-gaap_CashAndCashEquivalentsPeriodIncreaseDecrease" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DepreciationDepletionAndAmortization" xlink:label="us-gaap_DepreciationDepletionAndAmortization" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayable" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IncreaseDecreaseInDeferredLiabilities" xlink:label="us-gaap_IncreaseDecreaseInDeferredLiabilities" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IncreaseDecreaseInDeferredRevenue" xlink:label="us-gaap_IncreaseDecreaseInDeferredRevenue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IncreaseDecreaseInDepositOtherAssets" xlink:label="us-gaap_IncreaseDecreaseInDepositOtherAssets" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:label="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:label="us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" xlink:label="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_InterestPaidNet" xlink:label="us-gaap_InterestPaidNet" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IssuanceOfStockAndWarrantsForServicesOrClaims" xlink:label="us-gaap_IssuanceOfStockAndWarrantsForServicesOrClaims" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecurities" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecurities" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ProceedsFromIssuanceOfRedeemableConvertiblePreferredStock" xlink:label="us-gaap_ProceedsFromIssuanceOfRedeemableConvertiblePreferredStock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:label="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ProceedsFromWarrantExercises" xlink:label="us-gaap_ProceedsFromWarrantExercises" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_RepaymentsOfNotesPayable" xlink:label="us-gaap_RepaymentsOfNotesPayable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:label="us-gaap_ShareBasedCompensation" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SupplementalCashFlowInformationAbstract" xlink:label="us-gaap_SupplementalCashFlowInformationAbstract" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_NetIncomeLoss" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AdjustmentsNoncashItemsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AdjustmentsNoncashItemsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_DepreciationDepletionAndAmortization" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AdjustmentsNoncashItemsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AdjustmentsNoncashItemsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_IncreaseDecreaseInDeferredRevenue" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AdjustmentsNoncashItemsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_ShareBasedCompensation" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AdjustmentsNoncashItemsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_IssuanceOfStockAndWarrantsForServicesOrClaims" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AdjustmentsNoncashItemsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="clsn_DeferredFinanceCharges" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AdjustmentsNoncashItemsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_IncreaseDecreaseInDeferredLiabilities" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="us-gaap_IncreaseDecreaseInDepositOtherAssets" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="us-gaap_IncreaseDecreaseInAccountsPayable" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecurities" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="us-gaap_ProceedsFromIssuanceOfRedeemableConvertiblePreferredStock" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="us-gaap_ProceedsFromWarrantExercises" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="us-gaap_RepaymentsOfNotesPayable" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="us-gaap_CashAndCashEquivalentsPeriodIncreaseDecrease" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_SupplementalCashFlowInformationAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SupplementalCashFlowInformationAbstract" xlink:to="us-gaap_InterestPaidNet" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-13-earnout-milestone-liability-schedule-of-milestone-riskadjustment-assessment-details" xlink:href="clsn-20180331.xsd#statement-note-13-earnout-milestone-liability-schedule-of-milestone-riskadjustment-assessment-details" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-13-earnout-milestone-liability-schedule-of-milestone-riskadjustment-assessment-details" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_EstimatedTimeToAchieveTheMilestone" xlink:label="clsn_EstimatedTimeToAchieveTheMilestone" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_RiskAdjustedAssessmentOfEachMilestone" xlink:label="clsn_RiskAdjustedAssessmentOfEachMilestone" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationLiabilityMeasurementInput" xlink:label="us-gaap_BusinessCombinationContingentConsiderationLiabilityMeasurementInput" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_MeasurementInputDiscountRateMember" xlink:label="us-gaap_MeasurementInputDiscountRateMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_MeasurementInputTypeAxis" xlink:label="us-gaap_MeasurementInputTypeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_MeasurementInputTypeDomain" xlink:label="us-gaap_MeasurementInputTypeDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_MeasurementInputTypeDomain" xlink:label="us-gaap_MeasurementInputTypeDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_MeasurementInputTypeAxis" xlink:to="us-gaap_MeasurementInputTypeDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="srt_RangeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_MeasurementInputTypeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_MeasurementInputTypeDomain" xlink:to="us-gaap_MeasurementInputDiscountRateMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_MeasurementInputTypeAxis" xlink:to="us-gaap_MeasurementInputTypeDomain-default" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_RiskAdjustedAssessmentOfEachMilestone" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessCombinationContingentConsiderationLiabilityMeasurementInput" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_EstimatedTimeToAchieveTheMilestone" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-6-fair-value-of-financial-instruments-summary-of-investment-income-details" xlink:href="clsn-20180331.xsd#statement-note-6-fair-value-of-financial-instruments-summary-of-investment-income-details" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-6-fair-value-of-financial-instruments-summary-of-investment-income-details" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_InvestmentIncomeInterestAndDividend" xlink:label="us-gaap_InvestmentIncomeInterestAndDividend" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_InvestmentIncomeNonoperating" xlink:label="us-gaap_InvestmentIncomeNonoperating" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_RealizedInvestmentGainsLosses" xlink:label="us-gaap_RealizedInvestmentGainsLosses" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_InvestmentIncomeInterestAndDividend" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_RealizedInvestmentGainsLosses" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_InvestmentIncomeNonoperating" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-9-accrued-liabilities-other-accrued-liabilities-details" xlink:href="clsn-20180331.xsd#statement-note-9-accrued-liabilities-other-accrued-liabilities-details" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-9-accrued-liabilities-other-accrued-liabilities-details" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="us-gaap_AccruedLiabilitiesCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AccruedProfessionalFeesCurrent" xlink:label="us-gaap_AccruedProfessionalFeesCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ContractualObligation" xlink:label="us-gaap_ContractualObligation" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:label="us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OtherAccruedLiabilitiesCurrent" xlink:label="us-gaap_OtherAccruedLiabilitiesCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ContractualObligation" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AccruedProfessionalFeesCurrent" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OtherAccruedLiabilitiesCurrent" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AccruedLiabilitiesCurrent" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-12-stockbased-compensation-fair-value-of-option-assumptions-details" xlink:href="clsn-20180331.xsd#statement-note-12-stockbased-compensation-fair-value-of-option-assumptions-details" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-12-stockbased-compensation-fair-value-of-option-assumptions-details" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="us-gaap_EmployeeStockOptionMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_AwardTypeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="srt_RangeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember-default" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-condensed-consolidated-balance-sheets-current-period-unaudited" xlink:href="clsn-20180331.xsd#statement-condensed-consolidated-balance-sheets-current-period-unaudited" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-condensed-consolidated-balance-sheets-current-period-unaudited" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:label="us-gaap_AccountsPayableCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AccruedInvestmentIncomeReceivable" xlink:label="us-gaap_AccruedInvestmentIncomeReceivable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="us-gaap_AccruedLiabilitiesCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AdditionalPaidInCapitalCommonStock" xlink:label="us-gaap_AdditionalPaidInCapitalCommonStock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_Assets" xlink:label="us-gaap_Assets" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="us-gaap_AssetsCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AssetsCurrentAbstract" xlink:label="us-gaap_AssetsCurrentAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AssetsNoncurrent" xlink:label="us-gaap_AssetsNoncurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent" xlink:label="us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CommitmentsAndContingencies" xlink:label="us-gaap_CommitmentsAndContingencies" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CommonStockValue" xlink:label="us-gaap_CommonStockValue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DeferredRevenueCurrent" xlink:label="us-gaap_DeferredRevenueCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DeferredRevenueNoncurrent" xlink:label="us-gaap_DeferredRevenueNoncurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DepositsAssetsNoncurrent" xlink:label="us-gaap_DepositsAssetsNoncurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_Goodwill" xlink:label="us-gaap_Goodwill" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_GrantsReceivableCurrent" xlink:label="us-gaap_GrantsReceivableCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_Liabilities" xlink:label="us-gaap_Liabilities" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="us-gaap_LiabilitiesCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LiabilitiesCurrentAbstract" xlink:label="us-gaap_LiabilitiesCurrentAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OtherAssetsAbstract" xlink:label="us-gaap_OtherAssetsAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OtherLiabilitiesNoncurrent" xlink:label="us-gaap_OtherLiabilitiesNoncurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PreferredStockValue" xlink:label="us-gaap_PreferredStockValue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="us-gaap_PropertyPlantAndEquipmentNet" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="us-gaap_StockholdersEquity" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StockholdersEquityAbstract" xlink:label="us-gaap_StockholdersEquityAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StockholdersEquityBeforeTreasuryStock" xlink:label="us-gaap_StockholdersEquityBeforeTreasuryStock" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_TreasuryStockValue" xlink:label="us-gaap_TreasuryStockValue" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AssetsCurrentAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsCurrentAbstract" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsCurrentAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsCurrentAbstract" xlink:to="us-gaap_AccruedInvestmentIncomeReceivable" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsCurrentAbstract" xlink:to="us-gaap_GrantsReceivableCurrent" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsCurrentAbstract" xlink:to="us-gaap_AssetsCurrent" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AssetsCurrentAbstract" xlink:to="us-gaap_PropertyPlantAndEquipmentNet" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OtherAssetsAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherAssetsAbstract" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherAssetsAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherAssetsAbstract" xlink:to="us-gaap_Goodwill" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherAssetsAbstract" xlink:to="us-gaap_DepositsAssetsNoncurrent" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherAssetsAbstract" xlink:to="us-gaap_AssetsNoncurrent" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherAssetsAbstract" xlink:to="us-gaap_Assets" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_LiabilitiesCurrentAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_AccountsPayableCurrent" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_AccruedLiabilitiesCurrent" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_DeferredRevenueCurrent" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_LiabilitiesCurrent" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_DeferredRevenueNoncurrent" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_OtherLiabilitiesNoncurrent" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_Liabilities" xlink:type="arc"/>
    <link:definitionArc order="8" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LiabilitiesCurrentAbstract" xlink:to="us-gaap_CommitmentsAndContingencies" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockholdersEquityAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_PreferredStockValue" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_CommonStockValue" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_AdditionalPaidInCapitalCommonStock" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_StockholdersEquityBeforeTreasuryStock" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_TreasuryStockValue" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_StockholdersEquity" xlink:type="arc"/>
    <link:definitionArc order="8" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StockholdersEquityAbstract" xlink:to="us-gaap_LiabilitiesAndStockholdersEquity" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-condensed-consolidated-statements-of-comprehensive-loss-unaudited" xlink:href="clsn-20180331.xsd#statement-condensed-consolidated-statements-of-comprehensive-loss-unaudited" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-condensed-consolidated-statements-of-comprehensive-loss-unaudited" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxAttributableToParentAbstract" xlink:label="us-gaap_OtherComprehensiveIncomeLossNetOfTaxAttributableToParentAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OtherComprehensiveIncomeLossNetOfTaxAttributableToParentAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherComprehensiveIncomeLossNetOfTaxAttributableToParentAbstract" xlink:to="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherComprehensiveIncomeLossNetOfTaxAttributableToParentAbstract" xlink:to="us-gaap_NetIncomeLoss" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherComprehensiveIncomeLossNetOfTaxAttributableToParentAbstract" xlink:to="us-gaap_ComprehensiveIncomeNetOfTax" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-condensed-consolidated-statements-of-operations-unaudited" xlink:href="clsn-20180331.xsd#statement-condensed-consolidated-statements-of-operations-unaudited" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-condensed-consolidated-statements-of-operations-unaudited" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_GainLossFromValuationOfEarnoutMilestoneLiability" xlink:label="clsn_GainLossFromValuationOfEarnoutMilestoneLiability" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_EarningsPerShareBasicAndDiluted" xlink:label="us-gaap_EarningsPerShareBasicAndDiluted" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_EarningsPerShareBasicAndDilutedAbstract" xlink:label="us-gaap_EarningsPerShareBasicAndDilutedAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_EarningsPerShareBasicAndDilutedOtherDisclosuresAbstract" xlink:label="us-gaap_EarningsPerShareBasicAndDilutedOtherDisclosuresAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_GeneralAndAdministrativeExpense" xlink:label="us-gaap_GeneralAndAdministrativeExpense" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_InterestAndDebtExpense" xlink:label="us-gaap_InterestAndDebtExpense" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_InvestmentIncomeNonoperating" xlink:label="us-gaap_InvestmentIncomeNonoperating" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NonoperatingIncomeExpense" xlink:label="us-gaap_NonoperatingIncomeExpense" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingExpenses" xlink:label="us-gaap_OperatingExpenses" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingExpensesAbstract" xlink:label="us-gaap_OperatingExpensesAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:label="us-gaap_OperatingIncomeLoss" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OtherIncomeAndExpensesAbstract" xlink:label="us-gaap_OtherIncomeAndExpensesAbstract" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="us-gaap_OtherNonoperatingIncomeExpense" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:label="us-gaap_ResearchAndDevelopmentExpense" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_WeightedAverageNumberOfShareOutstandingBasicAndDiluted" xlink:label="us-gaap_WeightedAverageNumberOfShareOutstandingBasicAndDiluted" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OperatingExpensesAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_ResearchAndDevelopmentExpense" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_GeneralAndAdministrativeExpense" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_OperatingExpenses" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_OperatingIncomeLoss" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OtherIncomeAndExpensesAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherIncomeAndExpensesAbstract" xlink:to="clsn_GainLossFromValuationOfEarnoutMilestoneLiability" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherIncomeAndExpensesAbstract" xlink:to="us-gaap_InvestmentIncomeNonoperating" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherIncomeAndExpensesAbstract" xlink:to="us-gaap_InterestAndDebtExpense" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherIncomeAndExpensesAbstract" xlink:to="us-gaap_OtherNonoperatingIncomeExpense" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherIncomeAndExpensesAbstract" xlink:to="us-gaap_NonoperatingIncomeExpense" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OtherIncomeAndExpensesAbstract" xlink:to="us-gaap_NetIncomeLoss" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_EarningsPerShareBasicAndDilutedAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EarningsPerShareBasicAndDilutedAbstract" xlink:to="us-gaap_EarningsPerShareBasicAndDiluted" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_EarningsPerShareBasicAndDilutedOtherDisclosuresAbstract" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EarningsPerShareBasicAndDilutedOtherDisclosuresAbstract" xlink:to="us-gaap_WeightedAverageNumberOfShareOutstandingBasicAndDiluted" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-6-fair-value-of-financial-instruments-summary-of-cost-fair-value-and-maturities-of-shortterm-investments-details" xlink:href="clsn-20180331.xsd#statement-note-6-fair-value-of-financial-instruments-summary-of-cost-fair-value-and-maturities-of-shortterm-investments-details" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-6-fair-value-of-financial-instruments-summary-of-cost-fair-value-and-maturities-of-shortterm-investments-details" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_AvailableForSaleDebtSecuritiesAmortizedCostBasisCurrent" xlink:label="clsn_AvailableForSaleDebtSecuritiesAmortizedCostBasisCurrent" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_DebtSecuritiesAvailableforsaleMaturityAllocatedAndSingleMaturityDateRollingBetweenThreeAndTwelveMonthsAmortizedCost" xlink:label="clsn_DebtSecuritiesAvailableforsaleMaturityAllocatedAndSingleMaturityDateRollingBetweenThreeAndTwelveMonthsAmortizedCost" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_DebtSecuritiesAvailableforsaleMaturityAllocatedAndSingleMaturityDateRollingBetweenThreeAndTwelveMonthsFairValue" xlink:label="clsn_DebtSecuritiesAvailableforsaleMaturityAllocatedAndSingleMaturityDateRollingBetweenThreeAndTwelveMonthsFairValue" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_DebtSecuritiesAvailableforsaleMaturityAllocatedAndSingleMaturityDateRollingWithinThreeMonthsAmortizedCost" xlink:label="clsn_DebtSecuritiesAvailableforsaleMaturityAllocatedAndSingleMaturityDateRollingWithinThreeMonthsAmortizedCost" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_DebtSecuritiesAvailableforsaleMaturityAllocatedAndSingleMaturityDateRollingWithinThreeMonthsFairValue" xlink:label="clsn_DebtSecuritiesAvailableforsaleMaturityAllocatedAndSingleMaturityDateRollingWithinThreeMonthsFairValue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesSingleMaturityDate" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesSingleMaturityDate" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CertificatesOfDepositMember" xlink:label="us-gaap_CertificatesOfDepositMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="us-gaap_CorporateDebtSecuritiesMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="us-gaap_FinancialInstrumentAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain-default" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FinancialInstrumentAxis" xlink:to="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_FinancialInstrumentAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="us-gaap_CertificatesOfDepositMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_FinancialInstrumentAxis" xlink:to="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="us-gaap_CorporateDebtSecuritiesMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_AvailableForSaleDebtSecuritiesAmortizedCostBasisCurrent" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_DebtSecuritiesAvailableforsaleMaturityAllocatedAndSingleMaturityDateRollingWithinThreeMonthsAmortizedCost" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_DebtSecuritiesAvailableforsaleMaturityAllocatedAndSingleMaturityDateRollingWithinThreeMonthsFairValue" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_DebtSecuritiesAvailableforsaleMaturityAllocatedAndSingleMaturityDateRollingBetweenThreeAndTwelveMonthsAmortizedCost" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_DebtSecuritiesAvailableforsaleMaturityAllocatedAndSingleMaturityDateRollingBetweenThreeAndTwelveMonthsFairValue" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesSingleMaturityDate" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-7-fair-value-of-measurements-assets-and-liabilities-at-fair-value-on-a-recurring-basis-details" xlink:href="clsn-20180331.xsd#statement-note-7-fair-value-of-measurements-assets-and-liabilities-at-fair-value-on-a-recurring-basis-details" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-7-fair-value-of-measurements-assets-and-liabilities-at-fair-value-on-a-recurring-basis-details" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent" xlink:label="us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FairValueByMeasurementFrequencyAxis" xlink:label="us-gaap_FairValueByMeasurementFrequencyAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FairValueInputsLevel1Member" xlink:label="us-gaap_FairValueInputsLevel1Member" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FairValueInputsLevel3Member" xlink:label="us-gaap_FairValueInputsLevel3Member" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain" xlink:label="us-gaap_FairValueMeasurementFrequencyDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain" xlink:label="us-gaap_FairValueMeasurementFrequencyDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_FairValueMeasurementsRecurringMember" xlink:label="us-gaap_FairValueMeasurementsRecurringMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FairValueByMeasurementFrequencyAxis" xlink:to="us-gaap_FairValueMeasurementFrequencyDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_FairValueByMeasurementFrequencyAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueMeasurementFrequencyDomain" xlink:to="us-gaap_FairValueMeasurementsRecurringMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_FairValueByMeasurementFrequencyAxis" xlink:to="us-gaap_FairValueMeasurementFrequencyDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel1Member" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel3Member" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-12-stockbased-compensation-stock-option-and-restricted-stock-details" xlink:href="clsn-20180331.xsd#statement-note-12-stockbased-compensation-stock-option-and-restricted-stock-details" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-12-stockbased-compensation-stock-option-and-restricted-stock-details" xlink:type="extended">
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_RestrictedStockMember" xlink:label="us-gaap_RestrictedStockMember" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsForfeituresAndExpirations" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsForfeituresAndExpirations" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriod" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestExercisableAggregateIntrinsicValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestExercisableAggregateIntrinsicValue" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardEquityInstrumentsOtherThanOptionsAggregateIntrinsicValueOutstanding" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardEquityInstrumentsOtherThanOptionsAggregateIntrinsicValueOutstanding" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestExercisableWeightedAverageRemainingContractualTerm1" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestExercisableWeightedAverageRemainingContractualTerm1" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_AwardTypeAxis" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_RestrictedStockMember" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain-default" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriod" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" xlink:type="arc"/>
    <link:definitionArc order="7" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" xlink:type="arc"/>
    <link:definitionArc order="8" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:type="arc"/>
    <link:definitionArc order="9" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" xlink:type="arc"/>
    <link:definitionArc order="10" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue" xlink:type="arc"/>
    <link:definitionArc order="11" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod" xlink:type="arc"/>
    <link:definitionArc order="12" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice" xlink:type="arc"/>
    <link:definitionArc order="13" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsForfeituresAndExpirations" xlink:type="arc"/>
    <link:definitionArc order="14" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue" xlink:type="arc"/>
    <link:definitionArc order="15" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2" xlink:type="arc"/>
    <link:definitionArc order="16" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" xlink:type="arc"/>
    <link:definitionArc order="17" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardEquityInstrumentsOtherThanOptionsAggregateIntrinsicValueOutstanding" xlink:type="arc"/>
    <link:definitionArc order="18" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" xlink:type="arc"/>
    <link:definitionArc order="19" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" xlink:type="arc"/>
    <link:definitionArc order="20" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestExercisableWeightedAverageRemainingContractualTerm1" xlink:type="arc"/>
    <link:definitionArc order="21" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestExercisableAggregateIntrinsicValue" xlink:type="arc"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.celsion.com/20180331/role/statement-note-6-fair-value-of-financial-instruments-unrealized-losses-details" xlink:href="clsn-20180331.xsd#statement-note-6-fair-value-of-financial-instruments-unrealized-losses-details" xlink:type="simple"/>
  <link:definitionLink xlink:role="http://www.celsion.com/20180331/role/statement-note-6-fair-value-of-financial-instruments-unrealized-losses-details" xlink:type="extended">
    <link:loc xlink:href="clsn-20180331.xsd#clsn_AvailableforsaleSecuritiesDebtSecuritiesCurrentAccumulatedUnrealizedGainLoss" xlink:label="clsn_AvailableforsaleSecuritiesDebtSecuritiesCurrentAccumulatedUnrealizedGainLoss" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_DebtSecuritiesAvailableforsaleContinuousUnrealizedGainPositionLessThan12Months" xlink:label="clsn_DebtSecuritiesAvailableforsaleContinuousUnrealizedGainPositionLessThan12Months" xlink:type="locator"/>
    <link:loc xlink:href="clsn-20180331.xsd#clsn_DebtSecuritiesAvailableforsaleContinuousUnrealizedGainPositionLessThan12MonthsAccumulatedGain" xlink:label="clsn_DebtSecuritiesAvailableforsaleContinuousUnrealizedGainPositionLessThan12MonthsAccumulatedGain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain-default" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" xlink:type="locator"/>
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" xlink:type="locator"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="dei_LegalEntityAxis" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain-default" xlink:type="arc"/>
    <link:definitionArc order="0" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" xlink:type="arc"/>
    <link:definitionArc order="1" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_DebtSecuritiesAvailableforsaleContinuousUnrealizedGainPositionLessThan12Months" xlink:type="arc"/>
    <link:definitionArc order="2" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_DebtSecuritiesAvailableforsaleContinuousUnrealizedGainPositionLessThan12MonthsAccumulatedGain" xlink:type="arc"/>
    <link:definitionArc order="3" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:type="arc"/>
    <link:definitionArc order="4" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:type="arc"/>
    <link:definitionArc order="5" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="arc"/>
    <link:definitionArc order="6" xbrldt:closed="true" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="clsn_AvailableforsaleSecuritiesDebtSecuritiesCurrentAccumulatedUnrealizedGainLoss" xlink:type="arc"/>
  </link:definitionLink>
</link:linkbase>
