Background:　Molybdenum　disulfide　(MoS2)　has　been　widely　explored　for　biomedical　applications　due　to　its　brilliant　photothermal　conversion　ability.　In　this　paper,　we　report　a　novel　multifunctional　MoS2-based　drug　delivery　system　(MoS2-SS-HA).　By　decorating　MoS2　nanosheets　with　hyaluronic　acid　(HA),　these　functionalized　MoS2　nanosheets　have　been　developed　as　a　tumor-targeting　chemotherapeutic　nanocarrier　for　near-infrared　(NIR)　photothermal-triggered　drug　delivery,　facilitating　the　combination　of　chemotherapy　and　photothermal　therapy　into　one　system　for　cancer　therapy.　Results:　The　nanocomposites　(MoS2-SS-HA)　generated　a　uniform　diameter　(ca.　125　nm),　exhibited　great　biocompatibility　as　well　as　high　stability　in　physiological　solutions,　and　could　be　loaded　with　the　insoluble　anti-cancer　drug　erlotinib　(Er).　The　release　of　Er　was　greatly　accelerated　under　near　infrared　laser　(NIR)　irradiation,　showing　that　the　composites　can　be　used　as　responsive　systems,　with　Er　release　controllable　through　NIR　irradiation.　MTT　assays　and　confocal　imaging　results　showed　that　the　MoS2-based　nanoplatform　could　selectively　target　and　kill　CD44-positive　lung　cancer　cells,　especially　drug　resistant　cells　(A549　and　H1975).　In　vivo　tumor　ablation　studies　prove　a　better　synergistic　therapeutic　effect　of　the　joint　treatment,　compared　with　either　chemotherapy　or　photothermal　therapy　alone.　Conclusion:　The　functionalized　MoS2　nanoplatform　developed　in　this　work　could　be　a　potent　system　for　targeted　drug　delivery　and　synergistic　chemo-photothermal　cancer　therapy.　©　2019　The　Author(s).