Background and Aim: The highest incidence of HCC is in Asia, accounting for about 76% of all cases worldwide. In South East Asia, hepatitis B is the most common underlying cause. Although numerous associations between environmental factors (e.g. cigarette smoking, heavy alcohol drinking, male gender, older age), viral factors (e.g. viral load, active replication, genotype, core promoter mutations) and the development of HCC in chronic HBV infection have been identified, a clear understanding of the role of host genetics remains illusive. Bangladesh is a densely populated country with about 160 million populations, where HBsAg positivity in the healthy population is 5.4%. The aim is to evaluate the role of host IL28B (interleukin 28B; interferon lambda 3) single nucleotide polymorphism (SNP) in predicting hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) susceptibility. Methods: Single SNP in the IL28B gene (rs12979860C/T) were examined in 116 subjects (including 44 HBV-related HCC patients, 42 non-HCC patients with chronic hepatitis B and 30 healthy controls). The study was done at the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from January 2012 to December 2013. The polymorphism of IL28B rs12979860 was analyzed by a genotyping technique, based on polymerase chain reaction (PCR) followed by restriction enzyme analysis at the Department of Microbiology & Immunology, BSMMU. Results: The frequency of CC homozygosity was 70% in healthy controls and 45.5% in HCC, the difference being statistically significant (χ2 = 4.35, P = 0.03). Statistically significant difference was also seen between non-HCC patients with chronic hepatitis B (CHB) (69%) and HCC (45.5%) (χ2 = 4.35, P = 0.03). However, this significant finding was not seen between non-HCC patients with chronic hepatitis B (CHB) and healthy controls. Carriers of the minor T allele in rs12979860 had a higher risk of HCC compared with non-carriers (χ2 = 4.78, P = 0.02). Conclusion: Our results suggest that, T allele and non-CC genotypes have strong predictive effect of developing HCC and IL28Brs 12979860C/T polymorphism might influence susceptibility to HCC. The author has none to declare.