Objective：To elucidate the impact of small ubiquitin-related modifier（SUMO）modification on the protein levels and cellular localization of speckle type BTB/POZ protein（SPOP）and explore the correlation between sentrin-specific proteases 1 （SENP1）and SPOP in clear cell renal cell carcinoma（ccRCC）. Methods：Using wild type（WT）and Senp1 knockout murine embryonic fibroblasts（MEFs），we investigated the effects of Senp1 on Spop protein level and cellular localization. By comparing the protein expression levels of WT-Spop and its SUMO modification site mutants，the effects of SUMO modification on Spop protein levels were further confirmed. Proximity ligation assay（PLA）was employed to study the impact of Spop SUMOylation site mutation on the binding ability with small ubiquitin-related modifier 1（SUMO1）. Finally，the correlation between SENP1 and SPOP in ccRCC was examined utilizing datasets and ccRCC cell lines. Results：Senp1 knockout down-regulated the protein level and stability of Spop in MEFs without affecting its nuclear localization. Mutating the SUMOylation modification site of Spop attenuated its binding affinity with Sumo1，consequently leading to diminished protein levels. Notably，the expression of SENP1 and SPOP exhibited a positive correlation in ccRCC. Conclusion：Senp1 stabilizes Spop protein through deSUMOylation modification. The expression of SENP1 and SPOP is positively correlated in ccRCC.