Abstract Background: This research was conducted to explore the genetic association of interleukin-18 (IL-18) polymorphisms in promoter with ankylosing spondylitis (AS) in Chinese population using a case-control design.Methods: Polymerase chain reaction (PCR) and sequencing were used to complete the genotyping of IL-18 polymorphisms in 146 AS patients and 134 healthy controls. The genotype distribution of polymorphism was detected the status of Hardy-Weinberg equilibrium (HWE). The genotype and allele frequencies difference between the two groups was compared by chi-square test. Odds ratio (OR) with 95% confidence interval (95%CI) was calculated to express the association strength of AS. The linkage disequilibrium of IL-18 polymorphisms was investigated in AS occurrence by Haploview.Results: TT genotype and T allele of rs1946518 showed the significantly higher frequencies in AS patients than that of the controls (P=0.042, 0.026), which indicated that rs1946518 was obviously associated with AS risk (TT vs. GG: OR=1.993, 95%CI=1.021-3.891; T vs.G: OR=1.460, 95%CI=1.046-2.038). However, no significant association was found between rs187238 and AS. Moreover, the strong linkage disequilibrium was found and haplotype rs1946518T-rs187238C was a susceptible factor of AS (OR=1.638, 95%CI=1.017-2.639).Conclusion: IL-18 rs1946518 polymorphism may contribute to the susceptibility of individuals to AS in Chinese population, but not another polymorphism rs187238. The interaction of the two polymorphisms should be considered in AS etiology.