Cancer growth, metastasis and development are regulated by a number of genes, whose expression mediates important processes, including cellular plasticity, motility and internal interactions in the tumor microenvironment. The epithelial cell adhesion molecule (EpCAM) serves an important role in cell-cell migration and tumorigenicity, particularly metastasis. The aim of the present study was to measure EpCAM expression using immunohistochemistry and to investigate the association between clinicopathological features and prognosis in hepatocellular carcinoma (HCC). The results revealed that EpCAM expression may be a biomarker for poor prognosis in patients with HCC and may therefore be used to predict clinical outcome. The present study suggests that EpCAM expression in HCC can be considered as a routine biomarker for unfavorable prognosis and may provide a basis for the future development of anti-EpCAM-targeted therapy.