Viral infections cause approximately 12% of cancers worldwide and approximately 1. 3 million cancer- related deaths each year. However, representative in vivo models for all types of tumor viruses are lacking. Liver cancer is the fourth leading cause of cancer-related death in the world, and hepatocellular carcinoma (HCC) accounts for 80% of all liver cancer cases. Hepatitis B virus (HBV)-associated HCC is particularly a public health issue in China, which consists of more than 60% of domestic patients. Chronic HBV infection is the critical etiological factor for liver cancer. However, curable treatments for these patients are still lacking. The prerequisite for developing effective cancer drugs for HBV- associated HCC is to disrupt the mechanism of HBV interaction with the host. The mouse model of HBV-induced liver cancer has been remarkably advanced in recent decades, and multiple novel models have been developed by precision medicine. This review comprehensively summarizes the viral and oncogenic properties of in vivo models of HBV-induced HCC, with a focus on genetically engineered mouse and humanized mouse models. In addition, we discuss the benefits and caveats of each model and present a selection of the most important findings obtained from the respective systems.