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Background: Vitiligo is an acquired skin depigmentation disease. It can be misdiagnosed at an early stage and tend to relapse. Serum markers are essential to monitoring the progression of vitiligo. Exosomal miRNAs act as the communication mediator between melanocytes and immune cells. Our study aimed to use serum exosomal miRNAs as a reference for evaluating vitiligo progression. Methods: The miRNAs were extracted from the serum exosomes of ten progressive vitiligo patients (before and after treatment) and ten healthy individuals. We profiled miRNAs expression by RNA sequencing and screened out potential miRNAs and plotted their receiver operating characteristic (ROC) curves to explore their sensitivity and specificity as prognostic biomarkers in vitiligo progression. We examined the correlation between miRNA expression and the lesion area. Different databases were used to predict gene targets of miRNAs, which were analyzed by gene ontology and Kyoto encyclopedia of genes and genomes (KEGG). Results: Our results showed that 141 miRNAs were differentially expressed in serum exosomes of progressive vitiligo patients, and 365 miRNAs were differentially expressed in these patients after treatment compared to healthy individuals. The expression of hsa-miR-487b-3p was significantly lower in these patients compared to healthy individuals. Still, there was no difference in its levels in patients after corticosteroid treatment compared to healthy controls. ROC curve analysis (area under curve = 0.840) indicated that hsa-miR-487b-3p could serve as a biomarker for the prognosis of vitiligo progression. Its expression positively correlated with the lesion area. A total of 41 target genes of hsa-miR-487b-3p were predicted via different databases. KEGG pathways were enriched in phenylalanine metabolism, glycan degradation, and protein export. Conclusion: Serum exosomal hsa-miR-487b-3p can be a biomarker to detect vitiligo progression. The predicted target genes of hsa-miR-487b-3p were enriched in catabolism. Thus, its in progressive vitiligo may accelerate catabolism in melanocytes and cause its impairment. [ABSTRACT FROM AUTHOR]