Objective: To explore the diagnostic value of combined detection of total bilirubin (TBil), hyaluronic acid (HA) and apolipoprotein A1 (ApoA1) for chronic hepatitis B cirrhosis. Methods: A total of 68 patients diagnosed with chronic hepatitis B cirrhosis admitted to our hospital from January 2024 to February 2026 were enrolled as observation group, while another 72 patients with chronic hepatitis B in the same period were set as control group. The levels of TBil, direct bilirubin (DBil), aspartate aminotransferase (AST), alanine aminotransferase (ALT), ApoA1, apolipoprotein B (ApoB), HA and laminin (LN) were compared between the two groups. The correlation between these indicators and disease severity was analyzed. Receiver operating characteristic (ROC) curve was adopted to assess the diagnostic efficiency of single indicators as well as the combined detection of TBil, HA and ApoA1.Results: The levels of TBil and HA in observation group were significantly higher than those in control group, whereas ApoA1 level was markedly lower (P<0.05). Correlation analysis revealed that TBil and HA were positively correlated with disease severity, and ApoA1 was negatively correlated with disease severity (P<0.05). ROC curve analysis demonstrated that the area under curve (AUC) of combined TBil, HA and ApoA1 detection for diagnosing chronic hepatitis B cirrhosis was larger than that of each single index.Conclusion: Among multiple liver function and serum biochemical markers, TBil, HA and ApoA1 are closely associated with chronic hepatitis B cirrhosis. Combined detection of the three markers can elevate the laboratory diagnostic efficacy for chronic hepatitis B cirrhosis by reflecting bilirubin metabolism, hepatic fibrosis and hepatic synthetic function comprehensively.