The　therapeutic　efficacy　of　photosensitizers　in　photodynamic　therapy　(PDT)　largely　depends　on　the　reactive　oxygen　species　production,　types,　and　tissue　penetration　depth.　Particularly　in　malignant　tumors,　hypoxia　is　widely　recognized　as　a　major　obstacle　for　PDT.　Herein,　a　two-photon-excitable　heavy-atom　free　photosensitizer　PNF　is　designed.　PNF　can　be　used　as　a　type-I　photosensitizer　to　overcome　the　limitations　of　PDT　in　treating　hypoxic　tumors.　The　photosensitizer　PNF　exhibits　distinct　aggregation-induced　emission　characteristics　and　can　generate　O2　center　dot-　and　OH　center　dot　through　type　I　photochemical　processes　upon　808　nm　laser　irradiation.　The　two-photon-activated　PDT　induced　by　PNF　disrupts　cellular　redox　homeostasis,　and　increases　levels　of　lipid　peroxidation,　leading　to　apoptosis,　as　well　as　ferroptosis.　In　vitro　and　in　vivo　experiments　demonstrate　the　effectiveness　of　this　synergistic　treatment　strategy　in　inhibiting　the　growth　of　hypoxic　cancer　cells　and　tumors.　As　a　two-photon-activated　heavy-atom　free　AIEgen,　PNF　can　generate　O2　center　dot-　and　OH　center　dot　upon　808　nm　laser　irradiation　for　highly　efficient　type　I　photodynamic　therapy　of　hypoxic　tumors.　The　mechanism　of　aggregation-induced　ISC　of　PNF　is　revealed　by　Single-crystal　X-ray　diffraction　and　theoretical　calculations.　And　the　synergistic　of　apoptosis　and　ferroptosis　in　treating　hypoxic　tumors　is　effectively　induced　by　PNF.　image