Hepatocellular carcinoma (HCC) is a common malignant cancer worldwide characterized by high metastatic potential and poor prognosis following radical resection. Metastasin is a Ca(2+)-binding protein associated with tumor metastasis. However, the expression and function of metastasin remain unknown. In the present study, we found that the expression of metastasin was upregulated in HCC tissues and positively correlated with poor prognosis following radical resection. Ectopic expression of metastasin in vitro induced typical epithelial-mesenchymal transition (EMT) in Hep3B cells including higher capacity of both migration and invasion, increased expression of both Vimentin and N-cadherin and decreased expression of E-cadherin. Knockdown of metastasin produced the opposite results in MHCC97H cells, which indicates that metastasin promotes HCC progression via induction of EMT. SNAI1 expression was upregulated by enforced expression of metastasin and, consequently, suppressing upregulation of SNAI1 secondary to metastasin overexpression abolished EMT. Collectively, the present results suggest that metastasin leads to HCC EMT partly through upregulating SNAI1 and contributes to poor prognosis following radical liver resection.