To investigate the underlying molecular mechanism of tripartite motif-containing 58 (TRIM58) in the development of clear cell renal cell carcinoma (ccRCC), we explored TRIM58 expression and methylation in tumor tissues and the association with clinicopathological features and prognosis of tissue samples; Moreover, we examined the direct gene transcription of TRIM58-specific DNA demethyltransferase (TRIM58-TET1) by the CRISPR-dCas9 fused with the catalytic domain of TET1 and the biological functions in RCC cells. Here, TRIM58 is linked to clear cell renal carcinoma.