Abstract: Primary liver cancer represents a major health concern in China. The combina-tion of targeted therapy with immunotherapy has initiated a new era in liver cancer treatment. Currently, immunotherapy‑based combinational therapies are widely applied across all stages of liver cancer care, with notable improvements in neoadjuvant therapy, conversion therapy, postopera-tive adjuvant therapy, and locoregional treatments. These advancements have significantly improved patient outcomes. However, whether it is combination of targeted therapy with immunotherapy or dual immunotherapy for liver cancer, the overall response rate still needs to be further improved. Another crucial challenge remains in accurately selecting patients who will stand to benefit from these treatments. Importantly, tackling both primary and acquired drug resistance also presents an urgent and critical clinical and scientific issue in this field. Advancements in understanding tumor biology, discovering novel therapeutic targets, fostering pharmaceutical innovation and development, and decoding the mechanisms of drug sensitivity and resistance are all equally vital for the future breakthroughs in liver cancer treatments. The authors elaborate on the innovative progress of clinical and translational therapy research for liver cancer, in order to provide reference for the academic community to carry out related research.