Our results demonstrate that in RCC cells, ESRP1 promoter hypermethylation is accompanied by downregulation of its expression level; restoring ESRP1 expression can induce cell cycle G1-arrest and inhibit RCC cell proliferation by downregulating cyclin A2 expression; ESRP1-P-Luc2 may serve as a useful tool for monitoring the effects of DNMT inhibitor anticancer drugs at both the cellular level and in living animals, thereby providing a potential tool for high-throughput screening (HTS) of such drugs. This evidence concerns the gene ESRP1 and renal cell carcinoma.