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Abstract Background: Vitiligo is a progressive depigmentation of the skin with unclear etiology. Cell-mediated immunity has been suggested to play an important role in the pathogenesis of vitiligo’s progression. Melan-A has a high affinity for specific CD8+ T cells and is one of the critical markers for detecting damage to melanocytes. Aim: Our study aims to demonstrate the differences of Melan-A expression associated with apoptosis of melanocytes in patients with segmental vitiligo (SV) and those with non-segmental vitiligo (NSV). Methods: The subjects consisted of 64 patients diagnosed with vitiligo, of whom 33 were with NSV and 31 with SV. Skin biopsy and direct immunofluorescence were used to examine Melan-A, and the TUNEL method was performed to examine melanocyte apoptosis in both groups. Group comparisons were conducted using appropriate statistical methods. Results: Melan-A expression was significantly higher in the NSV group than in the SV group, and there was a significant difference between two groups (p = 0.001). The median of melanocyte apoptosis in the NSV group was relatively higher than in the SV group, and a significant difference was found between the two groups (p = 0.001). The Spearman’s rank correlation test between Melan-A expression and melanocyte apoptosis in the NSV group was 0.767 (76.7%) and showed a significant relationship (p <0.05). The same test in the SV group was 0.583 (58.3%) and showed a significant relationship (p <0.05). In both groups, the higher the Melan-A expression, the higher the melanocyte apoptosis. Conclusion: Melan-A expression and melanocyte apoptosis are correlated. The higher Melan-A expression and melanocyte apoptosis in NSV indicates more severe vitiligo disease compared to SV.