To investigate the regulatory role of orphan nuclear receptor ERRα in the progression of ccRCC, we conducted the stable knockdown of ERRα in Caki-1 with shRNA lentivirus. The total protein samples of Caki-1 with shCtrl and shERRα were collected and subjected to label free quantitative proteomics analysis based on LC-MS, the differentially expressed proteins were selected based on the p value and fold-changes between two groups. Then, bioinformatics analysis was performed to reveal the pathways and key factors related to ERRα in ccRCC