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However, driving factors about the activation and migration of CD8+ T cells remain obscure. In this study, we aim to identify differentially expressed genes (DEGs) and uncover potential factors that drive the disease in melanocyte-specific CD8+ T cells in vitiligo. A total of 1147 DEGs were found through transcriptome sequencing in CD8+ T cells from lesional skin of vitiligo patients and normal controls. Based on KEGG pathway enrichment analysis and PPI, 16 upregulated and 23 downregulated genes were identified. Ultimately, 3 genes were figured out after RT-qPCR verification. The mRNA and protein expression levels of PIK3CB, HIF-1<jats:italic>\u03b1<\/jats:italic>, and F2RL1 were all elevated in CD8+ T cells from peripheral blood in vitiligo. HIF-1<jats:italic>\u03b1<\/jats:italic>and PIK3CB were significantly increased in lesional skin of vitiligo. Two CpG sites of the HIF-1<jats:italic>\u03b1<\/jats:italic>promoter were hypomethylated in vitiligo CD8+ T cells. In conclusion, HIF-1<jats:italic>\u03b1<\/jats:italic>, F2RL1, and PIK3CB may act as novel drivers for vitiligo, which are all closely associated with reactive oxygen species and possibly contribute to the activation and\/or migration of melanocyte-specific CD8+ T cells in vitiligo. 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