Combination　therapy　offers　promising　opportunities　for　treating　advanced　non-small　cell　lung　cancer　(NSCLC).　Here,　we　established　a　chitosan-based　nanocomplex　CE7Q/CQ/S　to　deliver　molecular-targeted　drug　erlotinib　(Er),　Survivin　shRNA-expressing　plasmid　(SV),　and　photothermal　agent　heptamethine　cyanine　dye　(Cy7)　in　one　platform　for　simultaneous　near-infrared　(NIR)　fluorescence　imaging　and　triple-combination　therapy　of　NSCLC　bearing　epidermal　growth　factor　receptor　(EGFR)　mutations.　The　obtained　CE7Q/CQ/S　exhibited　favorable　photothermal　effects,　good　DNA　binding　ability,　and　pH/NIR　dual-responsive　release　behaviors.　The　conjugated　Er　could　mediate　specific　delivery　of　Cy7　to　EGFR-mutated　NSCLC　cells　to　enable　targeted　NIR　fluorescence　imaging　and　photothermal　therapy　(PIT).　The　in　vitro　and　in　vivo　results　showed　that　downregulation　of　Survivin　expression　and　the　photothermal　effects　could　act　synergistically　with　Er　to　induce　satisfactory　anticancer　effects　in　either　Er-sensitive　or　Er-resistant　EGFR-mutated　NSCLC　cells.　By　integrating　chemo/gene/photothermal　therapies　into　one　theranostic　nanoplatform,　CE7Q/CQ/S　could　significantly　suppress　EGFR-mutated　NSCLC,　indicating　its　potential　use　in　treating　NSCLC.　Statement　of　Significance　The　development　of　epidermal　growth　factor　receptor　tyrosine　kinase　inhibitors　(EGFR-TKIs)　has　improved　overall　survival　in　patients　with　NSCLC　driven　by　EGFR　mutations.　Unfortunately,　the　emergence　of　acquired　resistance　of　EGFR-TKIs　is　almost　inevitable　after　treatment.　Here,　we　constructed　a　NIR/pH　dual-responsive　nanocomplex　CE7Q/CQ/S　based　on　chitosan　which　could　integrate　targeted　near-infrared　fluorescence　imaging　and　chemo/gene/phototheramal　tri-therapies　together.　We　found　that　CE7Q/CQ/S　possessed　a　promising　outcome　in　fighting　against　EGFR-mutated　NSCLC.　The　inhibition　of　Survivin　expression　and　the　application　of　photothermal　therapy　could　act　synergistically　with　erlotinib　and　reverse　erlotinib　resistance.　The　results　of　this　work　suggested　that　this　chitosan-based　combination　therapeutic　nanoplatform　could　be　a　promising　candidate　for　NSCLC　treatment.　(C)　2020　Acta　Materialia　Inc.　Published　by　Elsevier　Ltd.　All　rights　reserved.