It has been confirmed that the following factors can be involved in inducing the resistance of HCC cells to molecularly-targeted drugs: 1) mutual compensatory effect between RTKs (receptor tyrosine protein kinases), MAPK, PI3K/AKT, HGF/cMET, and other related pathways (Gao et al., 2012; Fu et al., 2020); 2) mechanisms related to cell survival and anti-apoptosis (Yang X et al., 2021; Jia et al., 2021); 3) epithelial-mesenchymal transition (Chen et al., 2021; Xia et al., 2021); and 4) many factors and mechanisms such as cancer stem cells (Ko et al., 2020; Xia et al., 2020; Leung et al., 2021). This evidence concerns the gene AKT1 and hepatocellular carcinoma.