Studies have shown that visible light, specifically blue light, adversely affects cells, tissues, organs, and organisms. We investigated the effect of blue light on apoptosis, DNA integrity, and transcription of apoptotic and melanogenic genes using B16F1 melanoma cells. In this study, cells were irradiated with 2-50 W/m2 blue light (465 nm) for several time duration. Exposure to blue light decreased cell viability, but the pan-caspase inhibitor Z-VAD-FMK rescued blue light-induced cell death. Blue light also inhibited cell proliferation and arrested the cell cycle. Blue light-irradiated cells displayed several apoptotic features, like depolarized mitochondrial membranes and enhanced caspase-3 activity. Furthermore, blue light induced strand breaks in the genomic DNA in a dose- and time-dependent manner but did not induce the formation of cyclobutene pyrimidine dimers. The cell cycle inhibitor p21 and the pro-apoptotic gene Bax were upregulated in blue light-exposed cells, whereas the anti-apoptotic gene Bcl-2 and the apoptosis inhibitor survivin were downregulated. The key enzyme in melanin synthesis, tyrosinase, was upregulated after high-intensity (50 W/m2) blue light exposure and downregulated after low-intensity (0.2 W/m2) blue light exposure. Our study demonstrates that blue light triggers apoptosis and some of its effects are similar to those of ultraviolet radiation.