ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM), as a longstanding therapeutic approach, offers unique advantages and potential in the treatment of liver cancer. Recent studies have highlighted its role in preventing liver cancer progression by modulating key signaling pathways. TCM's multi-component, multi-target, and multi-pathway mechanisms of action have garnered significant attention in the medical community for their ability to address complex diseases like liver cancer. AIM OF THE STUDY: This review examines the current status and challenges in the application of TCM to regulate specific signaling pathways, including PI3K/Akt, NF-κB, TGF-β, Wnt/β-Catenin, and Notch, in liver cancer treatment. The goal is to further elucidate the critical roles of these pathways in liver cancer progression and provide new insights into the modern scientific interpretation of TCM. MATERIALS AND METHODS: Literature was retrieved from PubMed and Web of Science databases using keywords such as "traditional Chinese medicine," "Chinese medicine," and "signaling pathway." The articles reviewed span from 2004 to 2024. RESULTS: TCM demonstrates significant therapeutic and preventive effects in liver cancer by modulating signaling pathways involved in tumorigenesis. These pathways influence processes such as cell growth, invasion, proliferation, and inflammatory responses, contributing to the anti-cancer effects of TCM. CONCLUSION: By modulating key signaling pathways such as PI3K/Akt, NF-κB, TGF-β, Wnt/β-Catenin, and Notch, TCM plays an important role in both the treatment and prevention of liver cancer, offering a promising therapeutic approach grounded in traditional practices and modern scientific understanding.