Matrine has been reported to be an effective anti‑tumor therapy; however, the anti-metastatic effects of matrine on hepatocellular carcinoma (HCC) and the molecular mechanism(s) involved remain unclear. Therefore, the aims of the present study were to evaluate the effects of matrine on hepatoma and to determine the associated mechanism(s) involved. In the present study, matrine was confirmed to prevent the proliferation of HCC cells and it was observed that matrine also inhibited the migratory, and invasive capabilities of HCC at non‑toxic concentrations. Additionally, matrine increased epithelial‑cadherin expression and decreased the expression levels of vimentin, matrix metalloproteinase (MMP)2, MMP9, zinc finger protein SNAI1 and zinc finger protein SNAI2. These results indicate that the anti‑metastatic effect of matrine may be associated with epithelial‑mesenchymal transition (EMT). Furthermore, matrine can increase phosphatidylinositol 3,4,5‑trisphosphate 3‑phosphatase and dual‑specificity protein phosphatase PTEN (PTEN) expression and reduce phosphorylated‑protein kinase B (Akt) levels. In conclusion, these results suggested that matrine is a potential therapeutic agent that can suppress cancer‑associated invasion and migration via PTEN/Akt‑dependent inhibition of EMT.