In this paper, the solvent-dependent photosensitive behaviors of fullerene (C₆₀) were investigated in polar and nonpolar solvents by time-dependent density functional theory (TD-DFT) calculation. Based on the calculated physicochemical parameters on triplet state, it is revealed that excited-state C₆₀ only generates ¹O₂ via energy transfer in benzene, but can give birth to O₂^·− and ¹O₂ in water via energy transfer and electron transfer, respectively. Considering the fact that electron transfer is more favorable compared with energy transfer in polar biological systems, especially with the presence of electron donors, the O₂^·−-generating process will get predominant in physiological systems. These results account well for the experimental observations that O₂^·− and ^·OH are primarily responsible for the photoinduced DNA cleavage by C₆₀ under physiological conditions, whereas ¹O₂ plays a critical role in nonpolar solvents.