BACKGROUND: Chronic hepatitis B and C infections are major causes of morbidity and mortality in end-stage kidney disease (ESKD) patients on hemodialysis (HD). The Fibrosis-4 (FIB-4) score is a non-invasive method to evaluate chronic liver disease. However, it is unclear whether there is a connection between the FIB-4 score and major adverse cardiovascular events (MACEs) and mortality in patients on HD. This study investigates the relationship between FIB-4 scores, MACEs, and mortality in HD patients. METHODS: A 5-year retrospective study included 198 HD patients with chronic hepatitis B and C from Chang Gung Memorial Hospital. FIB-4 scores were categorized into high (>2.071), middle (1.030~2.071), and low (<1.030) tertiles for cross-sectional analyses. MACEs and mortality were tracked longitudinally. RESULTS: Patients with high FIB-4 scores had lower hemoglobin and albumin levels. Cox multivariate analysis showed that high FIB-4 scores (aHR: 1.589) and diabetes mellitus (aHR: 5.688) were significant factors for all-cause mortality. The optimal FIB-4 score for 5-year mortality was 2.942. FIB-4 scores were not significant for predicting 5-year MACEs. CONCLUSIONS: High FIB-4 scores are associated with increased 5-year all-cause mortality risk in HD patients with chronic hepatitis virus infection.