Taken together, these results provide a potential novel therapeutic strategy for HCV-infected patients by targeting the ER stress/PKA/GSK-3β-dependent Wnt/β-catenin pathway not only to eradicate viruses but also reverse the Wnt/β-catenin pathway that is widely thought to be a major pathway in HCC, which overcomes the issue of DAA treatment that Wnt/β-catenin signaling remains activated despite HCV clearance. Here, GSK3B is linked to hepatocellular carcinoma.