In this work, we have shown that metformin and simvastatin in combination decreased hepatoma cell proliferation arresting cell cycle in G0/G1, inhibited TCTP and mTOR pathway, increased tumor suppressor PTEN and promoted autophagy in Huh7.5 cells infected by HCV or non-infected and in primary hepatocytes, suggesting that these drugs should be tested as a chemo-preventive option in HCC. Here, PTEN is linked to neoplasm.