The results of the current study demonstrate that along with the activation of FOXO3a by salinomycin treatment or consistent activation of FOXO3a by transfected with FOXO3a-TM in HCC cells, the association of the β-catenin/TCF4 complex was decreased and TCF4 target genes such as ZEB1, c-Myc, CyclinD1 were inhibited, indicating that FOXO3a functions as an inhibitor of the classical Wnt signaling pathway. The gene discussed is ZEB1; the disease is hepatocellular carcinoma.