Abstract:Hepatocellular carcinoma is one of the most common malignancies and has become the second leading cause of tumor?related death. With its morbidity and mortality increasing annually, studies on its pathogenesis, progression, tumor immune microenvironment, and new drug development need to be advanced. Zebrafish has become an irreplaceable model organism to simulate human diseases because of its high similarity in the genome, tissues, and organs. Zebrafish hepatocellular carcinoma models, including genetic and xenotransplantation models, have played an important role in revealing the genetic etiology of hepatocellular carcinoma, disease progression, functions and interactions of immune cells in the tumor microenvironment, and drug screening. This article systematically reviewed the development history of zebrafish hepatocellular carcinoma models, compared the advantages and disadvantages of various models, highlighted the shortcomings of existing models, and proposed the possible development direction of this research field in the future. This article reviews the important research progress of zebrafish hepatocellular carcinoma models in recent years to provide a reference for hepatocellular carcinoma related research.