Apolipoprotein H (apoH) is produced by hepatocytes and also an acute phase protein in hepatitis B virus (HBV) infection. We found HBV and the large surface antigen upregulate apoH expression, which inhibits HBsAg secretion and then induces ER stress. ApoH is also found on several classes of lipoproteins, and is involved in lipid metabolism. However, the possible mechanisms behind the relationship between steatosis and HBV infection are unclear. Herein, we explore whether apoH regulates the development of fatty liver in chronic HBV infection.