Polyphyllin I inhibited HCC CSCs via Akt/GSK-3β/β-catenin signaling, as observed by ex vivo experiments, which revealed that polyphyllin I activated the Akt/GSK-3β-mediated ubiquitin-mediated proteasomal degradation of β-catenin and thereby inhibited the properties of HCC CSCs. The gene discussed is AKT1; the disease is hepatocellular carcinoma.