The purpose of this study is to investigate the association of IκBα with the development of ankylosing spondylitis (AS) in Taiwan. One hundred and fifty-four patients with AS and 112 unrelated healthy controls were enrolled in this study. The IκBα-881A/G, -826C/T, -550A/T, -519C/T, and -297C/T polymorphisms were determined by the polymerase chain reaction/restriction fragment length polymorphism method. This study demonstrated that the genotype frequencies of IκBα-826C/T and -826T/T, and allele frequencies of IκBα-826T were significantly higher in the patients with AS than in the controls. We also found that the estimated haplotype frequencies of IκBα-881A -826T -550A -519C -297C and IκBα-881A -826C -550A -519T -297C were significantly increased in the patient with AS in comparison with that of the controls. In contrast, the estimated haplotype frequency of IκBα-881A -826C -550A -519C -297C was significantly decreased in the patients with AS. This study demonstrates that IκBα-826T is associated with the development of AS. Furthermore, the IκBα-881A -826T -550A -519C -297C and IκBα-881A -826C -550A -519T -297C haplotypes are related to susceptibility to AS in Taiwan.