Hepatitis B virus (HBV) infection is well known as an important cause of the chronic liver disease. The screening of the genotype of certain cytokines might be helpful to predict the clinical outcome of an HBV infection. The present study investigates the relationship between the polymorphism and haplotypes of the Interleukin-1 (IL-1) gene family, including IL-1-alpha (IL-1A), IL-1-beta (IL-1B,) and IL-1 receptor antagonist (IL-1RN), with chronic HBV infection. A total of 297 chronic HBV and 333 matched on sex and age control individuals were genotyped using the standard sequence-specific-polymerase chain reaction primer (SSP-PCR) method. Four different haplotype analysis software packages were applied for data interpretation. The results showed excess genotype A1/A1 and A2/A2 at IL-1RN (40.2%, 39.9%), C/T at IL-1A-889 (55.6%), and C/C at IL-1B-511 (41.1%) in controls while A1/A1 at IL-1RN (59.3%), T/T at IL-1B-31 (46.5%), C/T at IL-1B + 3953 (65%), in chronic HBV infection cases. A total of 148 haplotypes were observed overall (96 in the case group and 89 in the control group). The haplotype combination of genotype A1/A1 at IL1-RN along with a C/T for all three IL-1B polymorphic positions and either C/T or T/T at the IL-1A-899 position may increase the probability of the chronic outcome for the HBV infection.