According to the results, after the overexpression of SALL4 in HCC cells, the protein expression of PTEN was significantly reduced, but the protein expressions of p-PI3K and p-AKT were remarkably raised, which indicated that SALL4 may activate the PI3K/AKT signaling pathway through targeting PTEN, thereby affecting the biological behavior of HCC cells. This evidence concerns the gene SALL4 and hepatocellular carcinoma.