Topical　chemotherapy　with　complementary　drugs　is　one　of　the　most　promising　strategies　to　achieve　an　effective　antitumor　activity.　Herein,　a　synergistic　strategy　for　hepatoma　therapy　by　the　combination　of　tumor　microenvironment-sensitive　polymer-doxorubicin　(DOX)　conjugate　thermogel,　containing　a　DNA　intercalator　DOX,　and　docetaxel　(DTX),　a　microtubule-interfering　agent,　was　proposed.　First,　cis-aconitic　anhydride-functionalized　DOX　(CAD)　and　succinic　anhydride-modified　DOX　(SAD)　were　conjugated　onto　the　terminal　hydroxyl　groups　of　poly(lactide-co-glycolide)-block-poly(ethylene　glycol)-block-poly(lactide-co-glycolide)　(PLGA-PEG-PLGA),　yielding　the　acid-sensitive　CAD-PLGA-PEG-PLGA-CAD　and　the　insensitive　SAD-PLGA-PEG-PLGA-SAD　conjugates,　respectively.　The　prodrug　aqueous　solution　exhibited　a　thermoreversible　sol-gel　transition　between　room　and　physiological　temperature.　Meantime,　appropriate　mechanical　property,　biodegradability,　as　well　as　a　sustained　release　profile　were　revealed　in　such　prodrug　thermogels.　More　importantly,　the　addition　of　DTX　to　the　DOX-conjugated　thermogels　(i.e.,　Gel-CAD　and　Gel-SAD)　was　verified　with　enhanced　curative　effect　against　tumor,　where　the　antitumor　efficacy　of　Gel-CAD+DTX　was　obviously　higher　than　the　other　groups.　A　reliable　security　in　vivo　was　also　showed　in　the　Gel-CAD+DTX　group.　Taken　together,　such　combination　of　tumor　microenvironment-labile　prodrug　thermogel　and　a　complementary　drug　exhibited　fascinating　prospect　for　local　synergistic　antineoplastic　therapy.　Statement　of　Significance　Multidrug　chemotherapy　with　synergistic　effect　has　been　proposed　recently　for　hepatoma　treatment　in　the　clinic.　However,　the　quick　release,　fast　elimination,　and　unselectivity　of　multidrugs　in　vivo　always　limit　their　further　application.　To　solve　this　problem,　a　synergistic　combination　of　tumor　microenvironment-sensitive　polymeric　doxorubicin　(DOX)　prodrug　thermogel　for　DNA　intercalation　and　a　microtubule-interfering　agent　docetaxel　(DTX)　is　developed　in　the　present　study　for　the　local　chemotherapy　of　hepatoma.　Interestingly,　a　pH-triggered　sustained　release　behavior,　an　enhanced　antitumor　efficacy,　and　a　favorable　security　in　vivo　are　observed　in　the　combined　dual-drug　delivery　platform.　Therefore,　effectively　combining　tumor　microenvironment-labile　polymeric　prodrug　thermogel　with　a　complementary　drug　provides　an　advanced　system　and　a　promising　prospect　for　local　synergistic　hepatoma　chemotherapy.　(C)　2018　Acta　Materialia　Inc.　Published　by　Elsevier　Ltd.　All　rights　reserved.