In summary, we aimed to investigate the role of CXCR4 in regulating cancer progression and drug resistance in ccRCC in vitro and in vivo, which not only broadened our knowledge in this field but provided evidences to support that CXCR4 could be used as a feasible biomarker for ccRCC diagnosis and prognosis. This evidence concerns the gene CXCR4 and nonpapillary renal cell carcinoma.