Mice have been widely used in the study of primary liver cancer owing to the close similarity of its genome to that of humans, its strong reproductive ability, the low cost of model construction, and the ease of genetic manipulation, including molecular mechanisms of pathogenesis and potential drug targets. Traditional animal models are increasingly falling short of meeting the needs of precision medicine research because of their inability to reproduce tumor microenvironment interactions and control the specificity of molecular subtypes. This study systematically compared the technical advantages of tail vein high-pressure injection, combined with transposon system (HTVI-TS), with traditional models in liver cancer research, and focused on the application value of the HTVI-TS model in the mechanism study of tumorigenesis and development, immunotherapy response prediction, and individualized evaluation of targeted drugs. This report presents a new research platform for precise diagnosis and treatment of primary liver cancer by simulating the heterogeneous evolution process of the cancer. The findings provide a theoretical basis for optimizing the selection of preclinical research models for liver cancer; the expansion potential of this technology in liver cancer research is outlined.