Introduction: Chronic hepatitis B (CHB) remains a major global health burden, often progressing to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The immune response, particularly the balance between pro-inflammatory cytokines like interferon-gamma (IFN-γ) and anti-inflammatory cytokines such as interleukin-10 (IL-10), plays a crucial role in disease progression. This study aimed to compare serum levels of IFN-γ and IL-10 in CHB patients with and without liver cirrhosis and to evaluate the IFN-γ/ IL-10 ratio as a marker of immune balance. Methods: A cross-sectional study was conducted involving 64 CHB patients at the General Hospital of West Nusa Tenggara, comprising 44 patients without cirrhosis and 20 with cirrhosis. Serum levels of IFN-γ and IL-10 were measured using ELISA. Data were analysed using the Mann-Whitney U tests to compare cytokine levels between groups. Results: Median IFN-γ levels were significantly higher in CHB patients with cirrhosis (2.56 pg/mL) compared to those without (1.165 pg/mL; p = 0.006). IL-10 levels were also elevated in the cirrhosis group, but the difference was not significant. The IFN-γ/IL-10 ratio tended to be higher in cirrhotic patients, but the difference was not statistically significant (p = 0.056). Conclusion: Elevated IFN-γ levels in cirrhotic CHB patients suggest a pro-inflammatory shift that may contribute to fibrosis progression. Although the IFN-γ/IL-10 ratio showed a trend toward immune imbalance, further longitudinal studies are needed to confirm these findings and evaluate their prognostic utility. © 2026, National Academy of Medicine. All rights reserved.