The Wnt/β-catenin signaling pathway plays a critical role in the development, progression, and therapy resistance of hepatocellular carcinoma (HCC). This pathway is essential for liver development, metabolic zonation, and regeneration. Abnormal activation of this pathway is a major cause of HCC tumorigenesis, progression, and resistance to therapy. The pathway is involved in various biological processes, including cell proliferation, invasion, and metastasis. It is also linked to the regulation of cancer stem cells and epithelial-mesenchymal transition (EMT), which are important in HCC progression. The pathway is also involved in glycolysis and angiogenesis, which are essential for HCC cell survival and growth. Additionally, the pathway is involved in hypoxia, which is a common feature of solid tumors, including HCC. The Wnt/β-catenin signaling pathway is also involved in therapy resistance, which is a major challenge in the treatment of HCC. Targeting this pathway may be a promising therapeutic approach for HCC patients. Various drugs and compounds have been developed to inhibit this pathway, including monoclonal antibodies, small molecule inhibitors, and natural bioactive compounds. These drugs have shown potential in preclinical studies, but more clinical trials are needed to evaluate their efficacy and safety in HCC treatment. The Wnt/β-catenin signaling pathway is a promising target for HCC therapy, and further research is needed to develop effective treatments for HCC patients.The Wnt/β-catenin signaling pathway plays a critical role in the development, progression, and therapy resistance of hepatocellular carcinoma (HCC). This pathway is essential for liver development, metabolic zonation, and regeneration. Abnormal activation of this pathway is a major cause of HCC tumorigenesis, progression, and resistance to therapy. The pathway is involved in various biological processes, including cell proliferation, invasion, and metastasis. It is also linked to the regulation of cancer stem cells and epithelial-mesenchymal transition (EMT), which are important in HCC progression. The pathway is also involved in glycolysis and angiogenesis, which are essential for HCC cell survival and growth. Additionally, the pathway is involved in hypoxia, which is a common feature of solid tumors, including HCC. The Wnt/β-catenin signaling pathway is also involved in therapy resistance, which is a major challenge in the treatment of HCC. Targeting this pathway may be a promising therapeutic approach for HCC patients. Various drugs and compounds have been developed to inhibit this pathway, including monoclonal antibodies, small molecule inhibitors, and natural bioactive compounds. These drugs have shown potential in preclinical studies, but more clinical trials are needed to evaluate their efficacy and safety in HCC treatment. The Wnt/β-catenin signaling pathway is a promising target for HCC therapy, and further research is needed to develop effective treatments for HCC patients.