Hepatoblastoma is the most common type of malignant liver tumor in children. While outcomes have been greatly improved in the past decades, the treatment of advanced hepatoblastoma has remained challenging. Enhancer of zeste homologue 2 (EZH2), a member of the polycomb group regulators of gene activity, is amplified and overexpressed in a variety of cancers. However, the role of EZH2 in hepatoblastoma has remained to be fully elucidated. The purpose of the present study was to investigate the expression patterns of EZH2 in hepatoblastoma cells and to assess the anti‑cancer effects of EZH2 depletion. Western blot analysis revealed that EZH2 expression was significantly higher in hepatoblastoma specimens compared with that in peri‑tumor tissues, while p27 was reduced in hepatoblastoma. Suppression of EHZ2 using lentiviral small hairpin RNA inhibited hepatoblastoma cell proliferation, induced cell cycle arrest in G1 phase and enhanced the expression of G1/S‑phase checkpoint protein p27. These results suggested that EZH2 may represent a potential diagnostic marker and therapeutic target for the treatment of hepatoblastoma.