Our study showed a novel crosstalk between KLF8 and Wnt/β-catenin signaling pathway, which plays important roles in HCC cells proliferation, furthermore, co-overexpression of KLF8 and β-catenin in human HCC samples indicated that KLF8-Wnt/β-catenin signaling pathway may provide novel reasoning for therapy of HCC. Here, KLF8 is linked to hepatocellular carcinoma.