Given　that　type　I　photosensitizers　(PSs)　possess　a　good　hypoxic　tolerance,　developing　an　innovative　tactic　to　construct　type　I　PSs　is　crucially　important,　but　remains　a　challenge.　Herein,　we　present　a　smart　molecular　design　strategy　based　on　the　Förster　resonance　energy　transfer　(FRET)　mechanism　to　develop　a　type　I　photodynamic　therapy　(PDT)　agent　with　an　encouraging　amplification　effect　for　accurate　hypoxic　tumor　therapy.　Of　note,　benefiting　from　the　FRET　effect,　the　obtained　nanostructured　type　I　PDT　agent　(NanoPcSZ)　with　boosted　light-harvesting　ability　not　only　amplifies　superoxide　radical　(O2•-)　production　but　also　promotes　heat　generation　upon　near-infrared　light　irradiation.　These　features　facilitate　NanoPcSZ　to　realize　excellent　phototherapeutic　response　under　both　normal　and　hypoxic　environments.　As　a　result,　both　in　vitro　and　in　vivo　experiments　achieved　a　remarkable　improvement　in　therapeutic　efficacy　via　the　combined　effect　of　photothermal　action　and　type　I　photoreaction.　Notably,　NanoPcSZ　can　be　eliminated　from　organs　(including　the　liver,　lung,　spleen,　and　kidney)　apart　from　the　tumor　site　and　excreted　through　urine　within　24　h　of　its　systemic　administration.　In　this　way,　the　potential　biotoxicity　of　drug　accumulation　can　be　avoided　and　the　biosafety　can　be　further　enhanced.　©　2024　The　Author(s).　Angewandte　Chemie　International　Edition　published　by　Wiley-VCH　GmbH.