The liver is an important organ that helps to maintain metabolism and detoxification function in the human body. Orthotropic liver transplantation (OLT) is recognized as the first therapeutic option for patients with end-stage liver disease or liver failure caused by acute or chronic liver failure or genetic defect. Hepatocyte transplantation, however, gradually emerges as a possible strategy to overcome the limitations of OLT, especially the lack of organ donors. To date, the feasibility of hepatocyte transplantation has been confirmed in various animal models, and clinical observations have demonstrated encouraging results in promoting liver regeneration or reducing liver fibrosis by autologous cell transplantation. This paper reviews the main clinical indications of hepatocyte transplantation, and focuses on obstacles and breakthroughs in new cell sources and transplantation technique in order to boost related research in this field, leading to wider application in clinic and providing fundamental solutions for the shortage of donor organs.