BackgroundVitiligo is an acquired, autoimmune, depigmented skin disease with unclear pathogenesis. Mitochondrial dysfunction contributes significantly to vitiligo, and mitophagy is vital for removing damaged mitochondria. Herein, using bioinformatic analysis, we sought to determine the possible role of mitophagy-associated genes in vitiligo and immune infiltration.MethodsMicroarrays GSE53146 and GSE75819 were used to identify differentially expressed genes (DEGs) in vitiligo. By crossing vitiligo DEGs with mitophagy-related genes, the mitophagy-related DEGs were identified. Functional enrichment and protein-protein intersection (PPI) analyses were conducted. Then, the hub genes were identified using two machine algorithms, and receiver operating characteristic (ROC) curves were generated. Next, the immune infiltration and its connection with hub genes in vitiligo were investigated. Finally, the Regnetwork database and NetworkAnalyst were used to predict the upstream transcriptional factors (TFs), microRNAs (miRNAs), and the protein-compound network.ResultsA total of 24 mitophagy-related genes were screened. Then, five mitophagy hub genes (GABARAPL2,SP1,USP8,RELA, andTBC1D17) were identified using two machine learning algorithms, and these genes showed high diagnostic specificity for vitiligo. The PPI network showed that hub genes interacted with each other. The mRNA expression levels of five hub genes were validated in vitiligo lesions by qRT-PCR and were compatible with the bioinformatic results. Compared with controls, the abundance of activated CD4+T cells, CD8+T cells, immature dendritic cells and B cells, myeloid-derived suppressor cells (MDSCs), gamma delta T cells, mast cells, regulatory T cells (Tregs), and T helper 2 (Th2) cells was higher. However, the abundance of CD56 bright natural killer (NK) cells, monocytes, and NK cells was lower. Correlation analysis revealed a link between hub genes and immune infiltration. Meanwhile, we predicted the upstream TFs and miRNAs and the target compounds of hub genes.ConclusionFive hub mitophagy-related genes were identified and correlated with immune infiltration in vitiligo. These findings suggested that mitophagy may promote the development of vitiligo by activating immune infiltration. Our study might enhance our comprehension of the pathogenic mechanism of vitiligo and offer a treatment option for vitiligo.