The liver is the major metabolic organ in the body and it plays a crucial regulatory role in maintaining homeostasis. In recent years, liver diseases have seriously threatened human health. However, the in vitro cultured cell lines or in vivo animal models cannot thoroughly reveal pathogenesis of human liver diseases and explore potential therapeutic targets effectively. Human liver organoids (HLOs), which are cell clusters differentiated from human cells through 3D culture in vitro, can mimic the structures and functions of the human liver in vitro. HLOs provide a new model for understanding the physiological structures and functions of the liver, simulating liver diseases in vitro, and exploring drugs for liver disease treatment. This review summarizes establishment strategies and applications of HLO models in recent years, and also discusses the defects of these models, which aim to provide a theoretical basis for the clinical applications of HLOs.