Objective To analyze the effect of Huganning tablets combined with polyene phosphatidylcholine in the treatment of hepatitis B cirrhosis. Methods A retrospective study was conducted to collect data on 97 patients diagnosed with hepatitis B cirrhosis who were admitted to our Hospital between February 2022 and April 2024. According to the difference in treatment plan, the patients were divided into the study group (48 cases) and the control group (49 cases). The control group was treated with polyene phosphatidylcholine, while the study group was treated with Huganning tablets and polyene phosphatidylcholine. All patients were treated for 6 months. The efficacy, adverse reactions, liver function, liver fibrosis status, immune function, and inflammation degree were compared between the two groups. Results The treatment efficacy rate of the study group was 93.75%, which was significantly higher than that of the control group’s 79.59% (P<0.05). After 6 months of treatment, the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) levels in the study group were lower than those in the control group (P<0.05). After 6 months of treatment, the levels of type III procollagen (PCIII), hyaluronic acid (HA), and laminin (LN) in the study group were lower than those in the control group (P<0.05). After 6 months of treatment, the CD3+, CD4+, and CD4+/CD8+ levels in the study group were higher than those in the control group (P<0.05). After 6 months of treatment, the levels of tumor necrosis factor-α (TNF-α), matrix metalloproteinase-2 (MMP-2), and interleukin-6 (IL-6) in the study group were all lower than those in the control group (P<0.05). There was no significant difference in the adverse reaction status between the two groups (P>0.05). Conclusion The combination of Huganning tablets and polyene phosphatidylcholine in the treatment of hepatitis B cirrhosis patients can improve the therapeutic effect, improve liver function, liver fibrosis, immune function, reduce inflammatory response, and does not increase significant adverse reactions.