Abstract: Objective To observe pathological changes in hepatitis B virus related acute-on chronic liver failure (HBV-ACLF) complicated with sepsis. Methods Liver specimens were selected from 50 cases of HBV-ACLF, made into paraffin slices, stained with HE staining, masson trichrome staining and CK-7 immunohistochemical staining and examined under a microscope. Results The characteristics of HBV-ACLF with sepsis were as followed: Massive/submassive necrosis was generated on cirrhosis with some residual nodules. There was different degree of ductular dilatation, cholestasis and epithelial cells atrophy in ductules on the margins of the residual nodules. Conclusions The characteristic of HBV-ACLF with sepsis was ductular cholestasis, which should be distinguished from other types of cholestasis.