Vitiligo is a serious cosmetic condition, mainly for individuals with dark skin. The patches of skin affected become white and usually have sharp margins. Often the patches begin on areas of skin that are exposed to the sun. It is more noticeable in people with dark skin. Vitiligo may result in psychological stress and those affected may be stigmatized. The exact cause of vitiligo is unknown. It is believed to be due to genetic susceptibility that is triggered by an environmental factor such that an autoimmune disease occurs. β-defensins are small antibiotic peptides that have direct antimicrobial, immune-enhancing and modulating and cytokine-like activity in the inflammatory signaling pathways. As a part of the innate immune system they mediate the first line of host defense and are encoded by the β-defensin genes localized in a human genome. HBD was studied as potential modulator of several autoimmune diseases. In this study, it was aimed to evaluate the association between human Beta-Defensin-1(-20 G/A) gene polymorphism with vitiligo. The study included 50 patients suffering from vitiligo and 50 healthy control subjects of matched age, sex, BMI of Egyptian origin. HBD (-20G/A) AA genotype and A allele showed significantly lower frequency in vitiligo patients when compared to the control subjects. AA genotype was significantly associated with lower VASI score.