Background <p>Vitiligo is a cutaneous disease caused by the destruction of functioning melanocytes. Cellular immunity is known to have a role in the pathogenesis of vitiligo. Macrophage migration inhibitory factor (MIF) is a potent activator of macrophages and is considered to play an important role in cell-mediated immunity.</p> Aims <p>We tried to investigate the association between MIF (rs755622) gene polymorphism and vitiligo susceptibility and its relationship to severity and clinical types of the disease.</p> Methods <p>Fifty patients with vitiligo and 50 healthy controls were included. Determination of MIF gene (rs755622) single nucleotide polymorphism was conducted using polymerase chain reaction (PCR).</p> Results <p>There were 18 males and 32 females who had vitiligo, together with 50 control participants of matched age and gender. Taking GG genotype and G allele as references, MIF GC, CC, (GC + CC) genotypes, and C allele demonstrated a substantially higher occurrence in all patients when compared to controls, with a higher risk of developing vitiligo within healthy control subjects.</p> Conclusions <p>To the best of our knowledge, this is the third study worldwide and the first from Egypt to investigate the association between MIF gene polymorphism (rs755622) with vitiligo susceptibility and severity, and it showed that MIF gene polymorphism (rs755622) may be considered a risk factor for vitiligo susceptibility. Moreover, it may be associated with higher disease extent.</p>