The level of CCHE1 expressed in all five HCC cell lines was significantly higher than the normal hepatocyte L02 cells. The higher expression of CCHE1 was significantly correlated with tumor number, tumor size and TNM stage. Multivariate analyses revealed that CCHE1 expression served as an independent predictor for overall survival. Moreover, the effect of CCHE1 on proliferation was evaluated by MTT assays, and cell apoptosis was detected by flow-cytometric analysis. Further experiments demonstrated that CCHE1 knockdown significantly promoted growth arrest and cell apoptosis. Importantly, we further confirmed that ERK/MAPK pathway was found to be inactivated in the HCC cells after CCHE1 knockdown.