Human leukocyte antigen (HLA)-B27 is strongly associated with the autoimmune disease ankylosing spondylitis (AS). Other autoimmune disease-associated genes, such as transporter associated with antigen processing (TAP) genes, could also influence AS susceptibility. In this study, we investigated the association of TAP1 and TAP2 polymorphisms in genetically homogenous Chinese AS patients. Six TAP1 single nucleotide polymorphisms (SNPs) and three TAP2 SNPs sites were analyzed in B27-positive AS cases, healthy B27-negative controls, and healthy B27-positive controls. In the allele and genotype analysis, the results indicated that TAP1 site 1910 allele G, genotype AG and TAP2 site 1693 genotype AA were associated with increased AS risk in a case-B27 negative control (p < 0.05). In the haplotype analysis, TAP1 SNP haplotype (GGGGGG, TAP1*020101) and TAP1-TAP2 SNP haplotypes (GGGGGG-GGG, TAP1*020101-TAP2*0101, and GGAAGG-GAG, TAP1*0101-TAP2*0102) increased AS risk in case-B27 negative control (p < 0.05). In contrast, TAP1-TAP2 SNP haplotype GGGGGG-GAG (TAP1*020101-TAP2*0102) was less common in cases than in B27-negative controls (p < 0.05). Moreover, TAP1-TAP2 SNP haplotype GGGAGG-GGG (TAP1*0301-TAP2*0101) was less common in cases than in B27-positive controls. The two haplotypes appeared to confer protection in AS (p < 0.05). These results suggest a potential mechanism of altered antigen-peptide selection and transport in AS pathogenesis.