Background: Vitiligo is a disorder of pigmentation characterized by the presence of depigmented skin macules due to chronic and progressive loss of melanocytes from the cutaneous epidermis. A number of polymorphisms within the gene coding for TNF-α has been described. Exchange of guanine by adenine at position –308 of the TNF-α promoter region is associated with higher serum levels of soluble TNF-α. Moreover, it has been associated with susceptibility to wide variety of diseases including vitiligo.Aim of work: The aim of the present study is to investigate the association between an inherited genetic polymorphism at TNF-α –308 (G→A) and vitiligo.Patients and methods: The study will be conducted on 100 middle aged (18-49 years) female patients with non-segmental vitiligo; and 110 age and sex matched controls, from each A 3ml blood sample was taken for detection of TNF-α -308 gene polymorphism by Restricted Fragment Length Polymorphism (RFLP) PCR.Results: A higher frequency of the TNF-α -308 A allele polymorphism (homozygous or heterozygous) in vitiligo patients than controls (P=.000) was found. No statistically significant difference was found between cases with normal genotype and those with mutant genotype as regard the age (P=.052), extent (P=.169), age of onset (P=.106), duration of illness (P=.435), type of vitiligo (P=.258), family history of vitiligo (P=.136), associations with other autoimmune conditions (P=.570), presence of amelanotic hair (P=.206), and response to treatment (P=.571). The odds ratio between individuals with normal genotype and those with the mutant genotype was 5.040 with the 95% confidence interval 2.771-9.168, which means that an individual with mutant gene is 5 times more susceptible to vitiligo than an individual with normal genotype. A statistically significant difference was noticed between vitiligo patients with heterozygous gene mutation and those with homozygous gene regarding the response to therapy, with the presence of poor/mild responses to therapy among patients with heterozygous genotype, while good response to therapy was seen in those with homozygous genotype (P=.001), while no statistically significant difference was noticed between the two patient groups regarding the age (P=.521), age of onset (P=.308), extent of the disease (P=.627), duration of illness(P=.778), associations with other autoimmune conditions (P=.307), family history of vitiligo (P=.744) and presence of amelanotic hair (P=.531). The odds ratio between cases of vitiligo with homozygous genotype and those with heterozygous genotype was 10.400 with the 95% confidence interval 4.101-26.377. This means that an individual with homozygous genotype is 10 times more susceptible to vitiligo than an individual with heterozygous genotype. Conclusion: A higher frequency of the TNF-α 308 gene polymorphism (homozygous or heterozygous) is observed in vitiligo patients than normal controls. An individual with TNF-α 308 gene polymorphism is five times more susceptible to vitiligo than normal individual. An individual with homozygous genotype is ten times more susceptible to vitiligo than individual with heterozygous genotype.