Objective To compare the clinical features of autoimmune hepatitis ( AIH) and primary biliary cholangitis ( PBC) , and to provide a reference for differentiation and early diagnosis of these two diseases. Methods A retrospective analysis was performed for the clinical data of 83 patients with AIH and 108 patients with PBC who were diagnosed and treated in Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2010 to February 2018, including age, sex, serum biochemical parameters, immunological indices, and liver pathology. The clinical features of AIH and PBC were compared. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results Most of the patients with AIH or PBC were female, with a peak age of onset of 40-60 years. There was no obvious specificity in the clinical features of AIH or PBC, with cardinal symptoms and signs of weakness, abdominal distension, jaundice, and poor appetite, and compared with the PBC group, the AIH group had a significantly higher proportion of patients with poor appetite ( 25% vs 14%, X2= 6. 52, P = 0. 011) . Compared with the PBC group, the AIH group also had significantly higher proportions of patients with liver cirrhosis ( 59. 0% vs 40. 7%, X2= 6. 23, P = 0. 012) and rheumatic diseases ( 23. 5% vs 15. 7%, X2= 7. 46, P = 0. 006) . Compared with the PBC group, the AIH group had significantly lower platelet count ( PLT) , alkaline phosphatase ( ALP) , gamma-glutamyl transpeptidase ( GGT) , immunoglobulin M, erythrocyte sedimentation rate ( ESR) , and complement C3 and significantly higher prothrombin time ( PT) , international normalized ratio ( INR) , and immunoglobulin G ( all P < 0. 05) . Compared with the AIH group, the PBC group had significantly higher positive rates of anti-mitochondrial antibody M2 ( 78. 8% vs 14. 8%, X2= 74. 70, P<0. 001) , anti-gp210 antibody ( 46. 4% vs 5. 3%, X2= 7. 31, P = 0. 007) , and anti-BCOADC-E2 PDC-E2 OGDC-E2 ( anti-3 E-BPO) antibodies ( 75. 0% vs 31. 6%, X2= 8. 73, P = 0. 003) . As for liver histological features, PBC was characterized by bile duct injury, including small cholangitis, biliary granuloma, absence of bile duct, and reactive hyperplasia of bile capillaries, while AIH was characterized by interface hepatitis ( X2= 31. 00 and 5. 88, P < 0. 001 and P = 0. 015) . Conclusion AIH and PBC often occur in women and lack specific clinical manifestations. PLT, ALP, GGT, PT, INR, ESR, complement, and immunoglobulins on admission, type of serological antibodies, and liver pathological features can be used for the differential diagnosis of AIH and PBC, and anti-3 E-BPO antibody can help with the diagnosis of PBC.