Background: Factors contributing to the pathogenesis of vitiligo and factors affecting its response to treatment are still a major area of debate. Aim of the work: The study aimed to assess the serum levels of tyrosinase and Micro-RNAs (miRNAs) gene polymorphism in a sample of Egyptian vitiligo patients, and to determine factors affecting the response of vitiligo to treatment. Subjects and methods: This prospective case-control interventional study included 212 nonsegmen-tal vitiligo patients and 96 control subjects. Before treatment, vitiligo was evaluated using Vitiligo Area Severity Index. Detection of miRNA 196a-2 polymorphism was done using PCRRFLP and serum tyrosinase was measured using ELISA. After treatment, patients were reevaluated clinically and serum tyrosinase levels were re-measured. Results: The tyrosinase levels were significantly elevated in patients. The TT genotype was the most prevalent one in the patients. The percentage of improvement showed a significant positive correl-ation with patients’ ages and age of the disease onset and a negative correlation with disease dur-ation, baseline VASI scores and serum tyrosinase levels. Conclusion: MiRNA 196a-2 C/T (11614913) gene polymorphism and the elevated serum tyrosinase levels might be related to the pathogenesis of vitiligo and may affect its therapeutic response.