This study aimed to compare the clinical characteristics of human fascioliasis and bacterial liver abscesses to provide a reference for the early and effective differentiation of these 2 diseases to avoid misdiagnosis. We retrospectively compared the epidemiological and clinical characteristics of 95 patients with human fascioliasis and 95 with bacterial liver abscess admitted to the First Affiliated Hospital of Dali University between January 2013 and March 30, 2023. The human fascioliasis group exhibited a higher proportion of female patients and a greater frequency of abdominal pain and lesions affecting both lobes of the liver. Additionally, eosinophil count, percentage of eosinophils, red blood cells, hemoglobin, total protein, albumin, carbohydrate antigen-125 (CA-125), CA-199, and CA-724 levels were elevated compared to the bacterial liver abscess group. Conversely, the proportion of patients with diabetes, duration of hospital stay, and the incidence of lesions affecting the right lobe of the liver, cavity formation, ascites, pleural effusion, white blood cells, total bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels were lower in the fascioliasis group compared to the bacterial liver abscess group. Furthermore, higher thrombin time and fibrinogen levels were observed in the fascioliasis group than in the bacterial liver abscess group (P < .05). Human fascioliasis predominantly occurs from August to November, while bacterial liver abscess exhibits a consistent incidence throughout the year. Human fascioliasis predominantly affects young women and demonstrates a seasonal pattern. It is associated with severe abdominal symptoms, widespread lesions, significantly elevated eosinophil levels, and seasonal incidence. Bacterial liver abscess predominantly affects elderly men with diabetes, and it is associated with localized lesions and severe inflammatory manifestations and occurs throughout the year.