The　development　of　efficient　photosensitizer　agents　is　crucial　for　cancer　phototherapy.　However,　conventional　photosensitizers　often　suffer　from　low　tumor　selectivity　and　poor　retention　in　tumor,　while　single-modal　therapies　such　as　photodynamic　therapy　(PDT)　or　photothermal　therapy　(PTT)　often　exhibit　diminished　efficacy.　Herein,　we　have　developed　a　H2S　activated　gold　nanoparticle　(AuNPs)-DNA　nanomachine　for　tumor　targeting,　fluorescence　imaging　and　combination　therapy　using　PDT　and　PTT.　The　nanomachine　consists　of　G-quadruplex　AS1411　aptamer　(serving　as　both　a　targeting　ligand　and　a　carrier　for　the　photosensitizer,　Ce6)　and　AuNPs　(serving　as　a　DNA　carrier　and　PTT　agent　after　response　to　H2S).　Upon　activation　by　H2S,　which　is　overexpressed　in　tumors,　the　system　releases　AS1411-Ce6　and　causes　aggregation　of　AuNPs,　resulting　in　an　absorbance　red　shift　to　the　near-infrared　(NIR)　region.　Upon　laser　irradiation,　the　released　AS1411-Ce6　generated　reactive　oxygen　species　for　PDT　(using　a　660　nm　laser),　while　the　aggregated　AuNPs　enhanced　the　PTT　effect　(using　an　808　nm　laser).　Both　in　vitro　and　in　vivo　experiments　demonstrated　that　this　dual-modal　phototherapy　significantly　inhibited　tumor　growth.　Therefore,　the　tumor　microenvironment　biomarker　responsive　nanomachine　represents　a　promising　nanoplatform　for　combinatorial　tumor　therapy.　©　2025　Elsevier　B.V.