Blue light, a high-energy radiation in the visible light spectrum, was recently reported to induce skin pigmentation. In this study, we investigated the involvement of TRPV1-mediated signaling along with OPN3 in blue light-induced melanogenesis, as well as its signaling pathway. Operating downstream target of OPN3 in blue light-induced melanogenesis, blue light activated TRPV1 and upregulated its expression, resulting in calcium influx. [Ca2+] induced activation of CaMKII and MAPK. It also downregulated clusterin expression, leading to the nuclear translocation of PAX3, ultimately affecting melanin synthesis. In addition, blue light interfered with autophagy-mediated regulation of melanosomes by decreasing not only the interaction between CLU and LC3B but the expression of ATF family. These findings demonstrate that the pigmenting effects of blue light are mediated by CaMKII- and MAPK-mediated signaling, as well as CLU-dependent inhibition of autophagy through OPN3-TRPV1-calcium influx, suggesting a new signaling pathway by which blue light regulates melanocyte biology. Furthermore, these results suggest that TRPV1 and CLU could be potential therapeutic targets for blue light-induced pigmentation due to prolonged exposure to blue light.