Background: Hepatocellular carcinoma (HCC) is one of most common causes for cancer-related death around the world. Epithelial cell adhesion molecule (EpCAM) is established as a vital prognostic factor for the human malignant tumors. However, the potential role of EpCAM in HCC has largely remained elusive. Herein we aimed to gain insight into the clinicopathological and prognostic role of EpCAM in HCC. Methods and materials: The PubMed, Web of Science, EMBASE and SCOPUS databases were systematically searched from their inception up to 5 December 4, 2017. The hazard ratio (HR) and odds ratio (OR) were respectively used as the effect size to explore the associations between EpCAM expression and the prognosis and clinicopathological features in HCC patients. Results: Sixteen studies recruiting 2488 HCC patients were included in the meta-analysis, of which the publication year ranging from 2011 to 2017. As a result, the pooled HR of 1.634 indicated that higher EpCAM expression was significantly associated with the shorter overall survival (OS) periods (95% CIs: 1.151-2.320; Z = 2.740, P = 0.006). Next, a meta-analysis of disease-free survival (DFS) was performed for the ten studies. Consequently, for the p-value less than 0.05 for the combined HR, the overexpression of EpCAM was significantly correlated with poorer DFS. Next, the results derived from our study suggest that the overexpression of EpCAM is associated with the clinicopathological features of HCC, including poorer tumor differentiation and high alpha-fetoprotein (AFP) levels. Conclusion: The results derived from our study suggest that the overexpression of EpCAM is associated with the clinicopathological features of HCC, including poorer differentiation and high AFP levels. More importantly, overexpression of EpCAM was confirmed as the unfavorable predictor for the shorter OS and DFS for HCC patients.