Taken together, our results successfully singled out six critical RBPs (CLK2, IGF2BP2, RNASE2, EZH2, PABPC1L, and RPL22L1) as a robust prognostic signature in ccRCC by external and internal verification, helping clinician predict patients’ survival status. This evidence concerns the gene RPL22L1 and nonpapillary renal cell carcinoma.