It is known that ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) shared a common genetic component. The gist of current study is to assess the role of IBD-associated autophagy gene IRGM on AS susceptibility in a Chinese Han population. A total of 1270 unrelated subjects (643 AS and 627 controls) were enrolled. Two tag single-nucleotide polymorphisms (SNPs) (rs10065172 and rs4958846) were selected and were genotyped by iMLDR Assay technology. Genotypes and haplotype analysis were conducted by using SPSS 16.0 and haploview 4.2 software. Among two tag SNPs of IRGM, no correlation was observed between rs10065172 and AS susceptibility. For rs4958846, genotype and allelic frequencies were marginally discrepant between female cases and controls before, not after, Bonferroni correction (P=0.049; P=0.031). Logistic regression analysis revealed that carriers with CT+TT or CT genotype had a significantly decreased risk for developing AS among female subjects when compared with CC genotype (OR=0.514, 95% CI=0.301-0.876, P=0.014; OR=0.518, 95% CI=0.297-0.902, P=0.020, respectively). Additionally, a risk haplotype rs4958846C-rs10065172C (OR=2.093, 95% CI=1.301-3.368) and a protective haplotype rs4958846T-rs10065172C (OR=0.652, 95% CI=0.441-0.964) were also identified to be associated with female AS. IBD-associated IRGM gene is also associated with AS susceptibility in the Chinese female population, indicating that autophagy pathway may involve in AS genetic predisposition.