It is important to design and synthesize safe and effective photosensitizers in photodynamic therapy for tumors. In this paper, a water-soluble fullerene photosensitizer (C60-OH-GSH) was synthesized by bonding reduced glutathione to fullerene C60 via nucleophilic addition reaction, and its chemical composition and structure were confirmed. C60-OH-GSH aggregates to nanoparticles of uniform size in aqueous solution, and it gives high stability in multiple physiological solutions, indicating its excellent biocompatibility. Under irradiation, C60-OH-GSH at low concentration of 1 ?mol/L can generate sufficient reactive oxygen species to induce cellular damage and apoptosis of various tumor cells, while in the dark it exhibit non negative effect on normal cells even at concentrations up to 50 ?mol/L, which makes it a promising photosensitizer for phototherapeutic application.