Vitiligo is a recalcitrant depigmentary autoimmune skin disorder. Hydroxychloroquine (HCQ) is an effective immunomodulatory drug which is widely used in treatment of autoimmune disorders. HCQ-induced pigmentation has been previously found in patients taking HCQ due to other autoimmune diseases. The present study aimed to determine whether HCQ improves re-pigmentation of generalized vitiligo. HCQ was orally administered 400 mg daily (6.5 mg/Kg of body weight) by 15 patients with generalized vitiligo (more than 10% involvement of body surface area) for three months. Patients were evaluated monthly and skin re-pigmentation was assessed using the Vitiligo Area Scoring Index (VASI). Laboratory data were obtained and repeated monthly. Fifteen patients (12 women and 3 men) with a mean age of 30.13±12.75 years were studied. After 3 months, the extent of re-pigmentation on all the body regions, including the upper extremities, hands, trunk, lower extremities, feet, and head and neck was significantly higher than the baseline (P value <0.001, 0.016, 0.029, <0.001, 0.006, 0.006, respectively). Patients with concomitant autoimmune diseases had significantly more re-pigmentation compared with others (P=0.020). No irregular laboratory data were observed during the study. HCQ could be an effective treatment for generalized vitiligo. The benefits are likely to be more evident in case of concomitant autoimmune disease. The authors recommend additional large-scale controlled studies to draw further conclusions.