Survival of patients with hepatocellular carcinoma (HCC) remains poor, which is largely attributed to active carcinogenesis. Accumulating evidence implies that long noncoding RNAs (lncRNAs) could play a pivotal role in cancer biology. However, the clinical valueand biological significance of CCHE1 in HCC carcinogenesis remains to be discovered. Expression of CCHE1was analyzed in 112 HCC tissues and cell lines by qRT–PCR. 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. To our knowledge, this is the first report showed that the role and the mechanism of CCHE1 in the progression of HCC. Together, these results suggest that lncRNA CCHE1 may serve as a candidate prognostic biomarker and target for new therapies in human HCC.