Prodrug therapy is one strategy to deliver anticancer drugs in a less reactive manner to reduce nonspecific cytotoxicity. A new multifunctional anticancer prodrug system based on water-dispersible fullerene (C60) aggregates is introduced; this prodrug system demonstrates active targeting, pH-responsive chemotherapy, and photodynamic therapeutic (PDT) properties. Incorporating (via a cleavable bond) an anticancer drug, which is doxorubicin (DOX) in this study, and a targeting ligand (folic acid) onto fullerene while maintaining an overall size of approximately 135 nm produces a more specific anticancer prodrug. This prodrug can enter folate receptor (FR)-positive cancer cells and kill the cells via intracellular release of the active drug form. Moreover, the fullerene aggregate carrier exhibits PDT action; the cytotoxicity of the system towards FR-positive cancer cells is increased in response to light irradiation. As the DOX drug molecules are conjugated onto fullerene, the DOX fluorescence is significantly quenched by the strong electron-accepting capability of fullerene. The fluorescence restores upon release from fullerene, so this fluorescence quenching–restoring feature can be used to track intracellular DOX release. The combined effect of chemotherapy and PDT increases the therapeutic efficacy of the DOX–fullerene aggregate prodrug. This study provides useful insights into designing and improving the applicability of fullerene for other targeted cancer prodrug systems.