Vitiligo is a potentially serious condition characterized by loss of melanin and death of melanocytes. To identify potential therapeutic targets for vitiligo, we conducted a microarray analysis of three human vitiligo specimens and paired adjacent normal tissues. Because we found that the fatty acid desaturase 1 (FADS1) gene was downregulated in vitiligo specimens, we carried out experiments to assess its role in melanocyte replication and survival. RT-qPCR was used to verify that FADS1 expression was lower in vitiligo-affected tissues and vitiligo melanocyte PIG3V cells than in matched controls or normal human epidermal PIG1 melanocytes. In addition, CCK-8, immunofluorescence, western blot and flow cytometry assay were used to detect the proliferation and apoptosis in PIG1 cells respectively. Overexpression of FADS1 promoted proliferation of PIG3V melanocytes, while FADS1 silencing inhibited proliferation and induced cell death in PIG1 melanocytes. Increased ROS generation; induction of mitochondrial-mediated apoptosis via upregulation of Bax and active caspases 3 and 9 and downregulation of Bcl-2; and cell cycle arrest via downregulation of c-Myc and Cyclin D1 and upregulation of p21 were all enhanced after FADS1 silencing in PIG1 melanocytes. These findings implicate FADS1 downregulation in the pathogenesis of vitiligo and may open new avenues for its treatment.