Background: Vitiligo is an autoimmune illness that causes uneven depigmentation by gradually destroying melanocytes in the skin. This disfiguring condition commonly affects the face and other visible regions of the body, causing psychological distress. Vitiligo usually appears in young people and progresses throughout their lives, resulting in a high disease burden and a poor quality of life. Objective: The aim of this study was better clarification the possible participation of interferon gamma (IFN-γ) in the pathogenesis of vitiligo. Patients and Methods: This case control study included 28 Patients with Vitiligo, and 28 healthy controls. Serum level of IFN-γ was measured by ELISA. Results: Age showed a non-significant correlation with serum IFN-γ in vitiligo and control group. Serum IFN-γ showed a significant strong positive correlation with the degree of severity in vitiligo group. In vitiligo patients' number of areas affected showed a significant positive correlation with serum IFN-γ. Serum IFN-γ also showed a significant positive very strong correlation with Psoriasis Area Severity Index (PASI) and Vitiligo Area Severity Index (VASI) score. Duration of the disease showed a significant correlation with serum IFN-γ only in vitiligo patients. Conclusion: It could be concluded that the augmented IFN-γ serum level is found in patients with vitiligo, marking the systemic inflammatory nature of these diseases. The study proved that IFN-γ serum level significantly increases with Vitiligo diseases activity.