Hepatocellular carcinoma (HCC) is a malignant tumor that arises from hepatocytes. Multiple signaling pathways play a regulatory role in the occurrence and development of HCC, with the Wnt signaling pathway being one of the primary regulatory pathways. In normal hepatocytes, the Wnt signaling pathway maintains cell regeneration and organ development. However, when aberrant activated, the Wnt pathway is closely associated with invasion, cancer stem cells(CSCs), drug resistance, and immune evasion in HCC. Among these factors, the development of drug resistance is one of the most important factors affecting the efficacy of HCC treatment. These mechanisms form the basis for tumor cell adaptation and evolution within the body, enabling continuous changes in tumor cells, resistance to drugs and immune system attacks, leading to metastasis and recurrence. In recent years, there have been numerous new discoveries regarding these mechanisms. An increasing number of drugs targeting the Wnt signaling pathway have been developed, with some already entering clinical trials. Therefore, this review encompasses the latest research on the role of the Wnt signaling pathway in the onset and progression of HCC, as well as advancements in its therapeutic strategies.