Background: Chronic hepatitis B virus (HBV) infection remains a major global health challenge and a leading cause of liver cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6), a key pro-inflammatory cytokine, plays an important role in immune regulation and hepatic inflammation. However, its relationship with HBV viral load and disease severity remains incompletely understood. Methods: A hospital-based cross-sectional study was conducted among 293 HBsAg-positive patients. Serum IL-6 levels were measured using ELISA, and HBV DNA was quantified using real-time quantitative PCR. Patients were stratified according to viral load. Statistical analyses included non-parametric tests, Spearman correlation, principal component analysis (PCA), and multiple linear regression. Results: The median age was 45 years (IQR: 34–57), among which 54.6% were male. The median HBV DNA was 3.37 log₁₀ IU/mL (IQR: 2.45–3.75), and IL-6 concentration was 2.38 log₁₀ pg/mL (IQR: 2.21–2.49). IL-6 levels increased significantly across viral load categories (p < 0.001) and were higher in HBeAg-positive patients (p = 0.002), with no significant differences across age, sex, or cirrhosis. IL-6 levels correlated with HBV DNA (r = 0.40, p < 0.001). PCA identified distinct viral-inflammatory and biochemical axes. Regression analysis confirmed HBV DNA as the significant independent predictor (β = 0.461, p < 0.001; adjusted R² = 0.206). Conclusion: IL-6 was closely associated with HBV DNA levels, while the association with conventional biochemical markers of hepatocellular injury was significantly less in this cohort, suggesting that IL-6 may serve as an adjunct biomarker of disease activity in patients with chronic hepatitis B.