Overexpression of multiple signaling pathways has been implicated in the pathogenesis of HCC, including epidermal growth factor (EGF), VEGF, Ras mitogen-activated protein kinase (MAPK), insulin-like growth factor receptor (IGFR), phosphoinositide 3-kinase (PI3K)/phosphatase, and tensin homolog (PTEN)/Akt/mammalian target of rapamycin (mTOR), hepatocyte growth factor/c-MET and Wnt/β-Catenin pathways providing a wide scope to hunt newer targets for HCC treatment. This evidence concerns the gene PTEN and hepatocellular carcinoma.