Abstract: Objective To investigate the relationship between the single nucleotide polymorphisms (SNP)-137G/C (rs187238) and-607C/A (rs1946518) in the promoter region of Interleukin-18 (IL-18) gene and chronic hepatitis B virus infection. Methods Case-control study was conducted among 264 chronic hepatitis B cases and 300 healthy controls seeking medical care in Guilin Municipal Center for Disease Control and Prevention and Affiliated Hospital of Guilin Medical College from March 2007 to October 2010. The SNP at the position of IL-18 gene promoter-137G/C (rs187238) and-607C/A (rs1946518) were detected by sequence specific primer-polymerase chain reaction (SSP-PCR). The genotype and allele frequencies were analyzed for both case group and control group. Results At rs1946518, the difference in the genotype and allele frequencies of IL-18 gene polymorphism between case group and control group was not significant (P0.05).but,at rs187238, G allele frequency was significantly higher (OR=1.353, 95% CI:1.009-1.815,P=0.043) in case group. Patients who carried rs187238 GG genotype had higher risk of suffering from chronic hepatitis B (OR=1.629,95% CI:1.152-2.305,P=0.006). Stratified analysis showed that rs187238 GC genotypes and C allele frequency were significantly associated in chronic hepatitis B patients who were HBeAg positive (P=0.022, P=0.011, respectively). Conclusion IL-18 gene promoter-137G/C (rs187238) polymorphism is correlated with chronic hepatitis B, and rs187238 GC genotypes and C allele frequency are respectively associated with chronic hepatitis B patients who are HBeAg positive.