Objective To analyze and summarize the research progression of phenotypic markers of hepatic sinusoidal endothelial cell （HSEC） and its role in the development and progression of the liver diseases. Methods Databases such as PubMed， Wanfang， CNKI， etc were retrieved for the latest articles on research advance in HSEC using “hepatic sinus endothelial cell”， “liver regeneration”， and “liver disease” as key words. All of the publications about studies on relation between HSEC and liver disease were reviewed and summarized. Results HSEC with specific cytoarchitectures and phenotypic markers was initially received “the message of damage” in the process of liver regeneration， hepatic immunological tolerance， hepatic fibrosis， and liver damage. Additionally， HSEC as the first barrier not only enabled liver to be protected but also was regarded as the first alternation of liver damage. Therefore， HSEC played a great important role in the process of the onset and progression of the liver disease. Conclusions The function of HSEC is complex. How do play a role and its the mechanism is unclarified， it is needed to be further studied.