Notwithstanding, our previously study results have confirmed that cytoplasmic AFP promoted proliferation and anti-apoptosis of HCC cells through activating growth signal and inhibiting apoptotic signal [21,39,40], but in this study, we found that HBx induced expression of AFPR and AFP to promote expression of Src in normal liver cells, activation of AFPR signal was a critical factor for HBx driving HCC occurrence. This evidence concerns the gene AFP and hepatocellular carcinoma.