We report the production of poly(lactic-co-glycolic acid) nanoparticles that encapsulate the photosensitizer meso-tetraphenylporpholactol. These nanoparticles are stable and nonphototoxic upon systemic administration. Upon cellular internalization, the photosensitizer is released from the nanoparticle and becomes highly phototoxic. Irradiation with visible light results in cell-specific killing of several cancer cell lines. Importantly, in vivo experiments show complete eradication of cancers in mouse models. The concept of photosensitizers with selective phototoxicity should have widespread applications in cancer therapy.