<i>In vitro</i> experiments demonstrated that knockdown or overexpression of G6PD markedly affected the proliferative, migratory, and invasive capacities of HCC cells.<h4>Conclusion</h4>This study reveals that bile acid metabolism promotes HCC progression by facilitating vascular network formation and establishing an immunosuppressive tumor microenvironment. The gene discussed is G6PD; the disease is hepatocellular carcinoma.