Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide, and its incidence and mortality are among the highest for many years. Due to its insidious onset, most patients are already at advanced stages when diagnosed. Improving the prognosis and survival rate of patients through conversion therapy has become a research focus lately. In recent years, with the continuous progress of biotechnology and drug development, new therapies represented by targeted and immunotherapy drugs have been widely used in HCC conversion therapy. Compared with other conversion therapy regimens, these drugs can effectively prolong the progression free survival and overall survival of patients and have advantages such as controllable adverse reactions. In addition, the combination of targeted drugs and immunotherapy drugs also plays a positive role in improving the survival benefit of HCC patients. This article aims to review the latest research progress of targeted therapy and immunotherapy in the first- and second-line treatments of HCC, and to discuss their safety and future development.