Autophagy is a cellular degradation process for cellular aggregates and unneeded cellular compartments including damaged mitochondria, ER, and peroxisomes. Melanosome is cellular organelle that is the cellular site of generation, storage and transports of melanin in melanocytes. Despite potential importance of autophagy, the role of autophagy in melanogenesis and melanosome autophagy are largely unknown. In here, we identified 3'-hydroxydaidzein (3'-ODI) as an autophagy inducer from a phytochemical library screening. Treatment with 3'-ODI significantly reduced alpha-MSH-mediated melanogenesis but efficiently increased autophagy both in melanoma cells and melanocytes. Furthermore, inhibition of autophagy significantly reduced the anti-melanogenic effects of 3'-ODI in alpha-MSH-stimulated melanoma cells. Taken together, these results suggest that autophagy mediates anti-melanogenic activity of 3'-ODI. (C) 2013 Published by Elsevier Inc.