Objectives This study evaluated the association among IL‐6(−572) and IL‐6(−597) genotypes, haplotypes, mRNA, and protein levels with hepatitis B virus (HBV)–Hepatocellular carcinoma (HCC) risk in India. Methods For this, 403 participants (153 controls, 61 inactive HBV‐carriers, 65 chronic‐active HBV patients, 63 HBV‐cirrhotics, and 61 HBV–HCC participants) were enrolled in the study. Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP), ELISA, and RT‐PCR methods were used for assessing polymorphism, protein, and the mRNA levels, respectively, of IL‐6. Results The study revealed that the IL‐6(−572) GC genotype shared a positive association with hepatitis among controls, and a negative association with cirrhosis and consequent HCC development among carriers. However, the CC genotype shared a significant negative association with cirrhosis among controls and carriers. The IL‐6(−597G>A), GA genotype acted as a potential protective factor for hepatitis, cirrhosis, and subsequent HCC development among carriers. The GA and CG haplotypes acted as a vital risk factor for HCC among controls and carriers. On the contrary, the CA haplotype was found to be a potential protective factor for HCC among carriers. Besides, the IL‐6 levels significantly increased with cirrhosis development, as compared to carriers and hepatitis subjects. Conclusions These preliminary findings indicate a potential role of IL‐6(−572/−597) genotypes in HBV disease pathogenesis in an Indian population. Am. J. Hum. Biol., 2014. © 2014 Wiley Periodicals, Inc.