The Ezh2 gene is an important member of the polycomb-group (PcG) family. As a newly identified oncogene, the expression of Ezh2 has been shown to be significantly increased in prostate cancer, breast cancer, renal cell carcinoma and hepatic cancer; however, a role for Ezh2 in the occurrence of glioma has not yet been reported. In this study, we found that the Ezh2 gene is highly expressed in U87 human glioma cells. Using RNA interference, we demonstrated that the downregulation of Ezh2 expression in U87 human glioma cells resulted in apoptosis and a cell cycle arrest in the G0/G1 phase. In addition, we found that silencing of the Ezh2 gene altered the mitochondrial membrane potential and promoted the release of cytochrome c from the mitochondria. Furthermore, the reduced expression of Ezh2 altered the Bax and Bcl-2 protein levels and led to the activation of caspase 9 and 3. These results indicate that the apoptosis induced in U87 human glioma cells by the silencing of the Ezh2 gene is related to the mitochondrial pathway.