Type I photodynamic therapy (PDT) exhibits outstanding therapeutic effects in hypoxic environments in tumors, but the design of type I photosensitizers (PSs), especially those with simple structures but dramatic properties, remains a challenge. Herein, we report a design strategy for developing type I PSs in one molecule with afterglow luminescence. As a proof concept, a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) PS (BIP) bearing water-soluble poly(ethylene glycol) (mPEG550) chains is synthesized, and BIP can self-assemble into nanoparticles (BIPNs). Interestingly, BIPNs exhibit an O2•--triggered afterglow luminescence, which is scarce, especially for BODIPY derivatives. BIPNs demonstrate outstanding type I dominant PDT at an ultralow dose under both hypoxic and normoxic environments, which can significantly inhibit tumor growth under irradiation. This work highlights a high-performance PS with afterglow luminescence and excellent PDT effects, underscoring the significant potential of versatile PSs in clinical tumor theranostics.