Objective To investigated the relationship between clear cell renal cell carcinoma（ccRcc） cells and α/β-hydrolase domain-containing 5（ABHD5） during migration and invasion in vitro. Methods The TCGA database was used to analyze the expression of ABHD5 in human ccRcc tissues and normal kidney tissues. After transfection of human ccRcc cell lines 786-O and Caki-1 with ABHD5-overexpressing lentivirus， the changes in ABHD5 expression were detected using real-time PCR and Western blot. Transwell assay and scratch assay were used to examine the effects of ABHD5 on cell migration and invasion in vitro. Results TCGA database showed that the expression of ABHD5 in ccRcc tissues was significantly decreased compared with normal renal tissues（P=0.000）， and the decrease was greater in recurrent metastatic tumors（P=0.007），which was significantly negatively correlated with the survival of the patients（P<0.001）. Transwell assay and scratch assay showed that ABHD5 overexpression significantly inhibited the migration and invasion of ccRcc cells in vitro（P<0.05）. Overexpression of ABHD5 inhibited renal cancer cell migration and invasion in vitro by influencing the Sting signaling pathway. Conclusion Lipid metabolism-related gene ABHD5 inhibited the migration and invasion of ccRcc cells in vitro.