The most enriched pathways were “T cell activation” and “cytokine-cytokine receptor interaction.” After PPI analysis, 22 hub genes related to ccRCC stood out, among which CD4, PTPRC, ITGB2, TYROBP, BIRC5, and ITGAM exhibited higher methylation levels, and BUB1B, CENPF, KIF2C, and MELK exhibited lower methylation levels in ccRCC tissues compared with paired tumor-free kidney tissues. Here, CENPF is linked to nonpapillary renal cell carcinoma.