In our study, we present a novel oncogene USP53 during ccRCC progression, in which USP53 expression decreases with increasing malignancy of ccRCC, regulating the NF‐κB signaling pathway to inhibit ccRCC proliferation and metastasis, thereby demonstrating that it functions as a potential therapeutic target in the tumorigenesis of ccRCC. The gene discussed is NFKB1; the disease is nonpapillary renal cell carcinoma.