Aim: The present study sought to investigate the therapeutic effect of resveratrol on clear cell renal cell carcinoma. Materials & methods: Cell Counting Kit-8 and 5-ethynyl-2 '-deoxyuridine assays were used to verify the cell proliferation. Transwell, real-time quantitative transcription PCR, western blot and beta-galactosidase staining were used to verify the migration, macrophage polarization and senescence. The tumor inhibitory effect of resveratrol on clear cell renal cell carcinoma was verified in vivo. Results: This study confirmed that resveratrol could affect the stability of CCNB1 mRNA mediated by RBM15 and inhibit the cancer process by inhibiting the expression of EP300/CBP from the perspective of cell senescence. Conclusion: Resveratrol is able to treat clear cell renal cell carcinoma through RBM15-induced cell senescence. A recent study has shown that resveratrol RBM15 mRNA stability and suppressing cancer cell proliferation, offering a promising therapeutic approach for kidney cancer. #Resveratrol #Kidney Cancer