Cellular phototoxicity induced by UVA irradiation and its potential application to therapy has been reported. In the present study, the induction of apoptosis induced by β-carotene and dimethyl tetrasulfide (Me2S4) assisted by UVA irradiation in HL-60 cells was assessed. β-carotene assisted by UVA significantly decreased the cell viability and induced DNA fragmentation in HL-60 cells. Me2S4 combined with β-carotene and assisted by UVA significantly inhibited the cell viability, and enhanced the caspase-3 activity which was completely inhibited by N-acety-L-cysteine. β-carotene was significantly degraded by UVA, but this was not accelerated by Me2S4 in a cell culture system. The photodegradation products of β-carotene prepared by UVA irradiation regardless of the addition of Me2S4 showed lower cytotoxicity than β-carotene itself in HL-60 cells. These results suggest that the ROS-and caspase-3-dependent apoptosis induced by β-carotene and Me2S4 assisted by UVA was due to a synergistic action rather than to the sole effect of the photodegradation products of β-carotene in HL-60 cells.