Collectively, these results suggested that the knockdown of mortalin blocked the PI3K/Akt pathway, which in turn inactivated the VEGF/VEGFR, GM-CSF, and β-catenin/antiapoptosis signaling pathways, leading to the attenuation of angiogenesis and sorafenib resistance in HCC cells. This evidence concerns the gene AKT1 and hepatocellular carcinoma.