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Vitiligo is a common skin disorder that is caused by selective destruction of melanocytes, resulting in disfiguring loss of pigment. There are convincing evidences that cytokines and T cell mediated immunity may have a role in its pathogenesis. Given the fact that cytokine production is under genetic control, in this study, we have investigated IFN-gamma +874 T/A and TNF-alpha -308 G/A gene polymorphisms in a total of 176 vitiligo patients and 545 controls. IFN-gamma +874 T/A and TNF-alpha -308 G/A gene polymorphisms were genotyped via Allele Specific Oligonucleotide PCR (ASO-PCR) method. The results showed that the TNF-alpha -308 G/A polymorphism was more common in vitiligo patients than controls (P = 0.0004). This difference was only significant between female patients and controls (P < 0.0001), while there was no significant difference between male patients and male controls (P = 0.90). The distribution of IFN-gamma genotypes in vitiligo patients did not differ significantly from that in control subjects (P = 0.56). Since the presence of A nucleotide at position -308 of TNF-alpha gene is associated with increased cytokine production, therefore, the higher frequency of TNF-alpha -308 A allele in vitiligo patients compared to controls may be considered as a genetic susceptibility factor towards the development of vitiligo.