Although enhancer of zeste homolog 2 (EZH2) has been reported as an independent prognostic factor inrenal cell carcinoma (RCC), little is known about the exact mechanism of EZH2 in promoting the genesis ofRCC. However, several studies have shown that dysregulation of the Wnt/β-catenin signaling pathway plays acrucial role. Therefore, we determined whether EZH2 could affect ACHN human RCC cell proliferation andinvasion via the Wnt/β-catenin pathway. In the present study, we investigated the effects of short interferingRNA (siRNA)-mediated EZH2 gene silencing on Wnt/β-catenin signaling in ACHN cells. EZH2-siRNA markedlyinhibited the proliferation and invasion capabilities of ACHN, while also reducing the expression of EZH2,Wnt3a and β-catenin. In contrast, cellular expression of GSK-3β (glycogen synthase kinase-3β), an inhibitorof the Wnt/β-catenin pathway, was conspicuously higher after transfection of EZH2 siRNA. These preliminaryfindings suggest EZH2 may promote proliferation and invasion of ACHN cells via action on the Wnt/β-cateninsignaling pathway.