In our current study, PI3K inhibition induced by LY294002 decreased active β-catenin expression through decreases of p-GSK3β-Ser9 in HCC cells, whereas activation form of PIK3CA (PI3KE545K) increased active β-catenin expression through increases of p-GSK3β-Ser9 in mouse liver tumors, suggesting that PI3K/Akt pathway regulated Wnt/β-catenin pathway through GSK3β. The gene discussed is PIK3CA; the disease is hepatocellular carcinoma.