Our findings conformed that KLF7/VPS35 axis observably activated β-catenin signaling through interacting with Ccdc85c, to promote cell proliferation, colony formation, invasion and cell cycle of HCC cells, which was verified by detection active β-catenin expression following alteration of KLF7 and VPS35 expression, and biological functions studies treated with β-catenin inhibitor in HCC cell lines. Here, CCDC85C is linked to hepatocellular carcinoma.