Polymorphisms in the gene promoter can lead to different levels of cytokine expression and let some individuals have unique immune responses. Therefore, the association of single nucleotide polymorphism of interleukin (IL)-18 promoter region in chronic hepatitis B virus (HBV) infection was examined. The results demonstrated the significant involvement of genotype A/A at position -607 in patients (n = 140) when compared with healthy individuals (n = 140) [OR (95% CI) = 2.62 (1.36-5.09), P(c)= 0.009]. The frequencies of -607A/A, C/A, C/C genotypes were 27.86%, 48.57% and 23.57% in chronic HBV patients and 12.80%, 59.30% and 27.90% in healthy controls, respectively. No significant association at the position -137 was found between the two groups. The frequencies of -607A/-137G haplotype homozygosity were higher in the chronic HBV patients (17.14%) than in the controls (8.57%) [OR (95% CI) = 2.21 (1-4.93), P = 0.05], although this was not statistically significant when corrected for multiple comparison (P(c)= 0.40). In conclusion, this study proposes that A/A genotype at position -607 in IL-18 gene can be used as a new genetic maker in Thai population for predicting chronic hepatitis B development.