In this research, we found that upregulation of PTEN and phosphorylation inhibition of EGFR via deletion of EZH2 could reduce subsequently renal fibrosis after I/R or FA injury, and vitro experiments confirmed that EZH2 binding to the PTEN promoter to regulate its transcription in HK2 cells under H2O2 injury. This evidence concerns the gene EGFR and renal fibrosis.