In this study, we found that co-culture of QSG-7701 (human hepatocyte) with HepG2 (hepatoma cell line) increases QSG-7701’s proliferation, and that AKR1B10-S1P signaling is necessary for this increase in proliferation; up-regulation of AKR1B10 and S1P levels was also confirmed in PHC tissues. This evidence concerns the gene MBTPS1 and hepatocellular carcinoma.