The FAS/FASLG system plays a key role in regulating apoptosis. Previous findings have shown that CD4-dependent destruction of melanocytes is partially inhibited by blocking FAS-FASLG interactions in autoimmune vitiligo. Functional polymorphisms of the FAS and FASLG genes can alter their transcriptional activities. In a hospital-based case-control study of 750 vitiligo patients and 756 controls, we genotyped the FAS-1377 G>A, FAS-670 A>G, and FASLG-844 T>C polymorphisms and assessed their association with the risk of vitiligo. We found that a significantly increased risk of vitiligo was associated with the FAS-1377 AA genotype (adjusted odds ratio (OR), 1.49; 95% confidence interval (CI), 1.07-2.08) and the FAS-1377 AG genotype (adjusted OR, 1.31; 95% CI, 1.05-1.63) when compared with the FAS-1377 GG genotype. However, no evident risk was associated with FAS-670 G>A genotypes. In the combined analysis of the two variant alleles of FAS, genotypes with 3 to 4 risk alleles were associated with an increased risk of vitiligo compared with those having 0-2 variants (adjusted OR, 2.87; 95% CI, 1.90-4.32). In conclusion, genetic variants in the FAS gene may affect the risk of vitiligo in Chinese populations.