Abstract:Hepatocellular carcinoma（HCC）is one of the most prevalent malignant tumors globally，characterized by its high degree of malignancy，challenging treatment options，and poor prognosis. Chimeric antigen receptor T cell（CAR-T）therapy，as an innovative therapeutic strategy，has advanced to the fifth generation and demonstrates significant potential for the treatment of primary liver cancer. Glypican-3（GPC3），which is specifically overexpressed in HCC with a high detection rate even in the early stages of liver cancer，serves as an ideal target for CAR-T therapy. Nevertheless，this approach still encounters obstacles such as off-target effects，suppression by the tumor microenvironment，and CAR-T exhaustion. This article emphasizes the synergistic application of CAR-T with emerging technologies and the advancements in new drug development，providing a comprehensive review of the research endeavors conducted by scholars both domestically and internationally in recent years to enhance the therapeutic efficacy of CAR-T therapy.