Hepatocellular carcinoma(HCC)is the most common type of primary liver cancer. The boom in novel immunotherapies has topped the most remarkable progress in HCC treatment in the past decade. As members of the immune system，natural killer(NK) cells play a vital role in anti-tumor immunity. Chimeric antigen receptor(CAR)-NK cell therapy is a new type of tumor immunotherapy， in which NK cells are genetically engineered to specifically recognize tumor-associated antigens to produce more precise and efficient anti -tumor efficacy. Focusing on CAR targets and related immune checkpoints，this review summarizes the challenges and possible solutions for CAR-NK in HCC treatment. Furthermore，it discusses potential strategies for boosting the efficacy of CAR-NK.