Abstract: Objective To compare the characteristics of intrahepatic ductular proliferation in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and end-stage of HBV-associated liver cirrhosis. Methods Select liver pathological specimens from 20 cases of HBV-ACLF and 25 cases of hepatitis B liver cirrhosis patients with end-stage before liver transplantation were obtained and made into paraffin slides. Then HE staining and anti-cytokeratin-7 (CK-7) immunohistochemistry staining were carried out, followed by morphological observation and comparative analysis. Results In liver samples from HBV-ACLF group, we observed a large number of CK-7 positive proliferating ductules, extruding into the center of necrotic zone around portal tracts in the peripheral of massive or submassive necrotic zone. And we clearly recognized differentiated intermediate hepatocytes; while in end-stage of HBV-associated liver cirrhosis group, we found a small amount of proliferating ductules encircling the surface of cirrhotic nodules and focal ductular reaction around focal inflammatory necrotic area, and intermediate hepatocytes were rarely found. Conclusions Ductular proliferation of HBV-ACLF and end-stage of HBV-associated liver cirrhosis patients displayed disparate patterns, which furtherly clarifies the distinction in liver pathology between the two groups.