TNFRSF17 is preferentially expressed in mature B lymphocytes, and may be important for the development of B cells. TNFRSF17 is selected as a candidate susceptibility gene to IBD pathogenesis by our cDNA microarray analysis, and we showed the specific expression of TNFRSF17 in resting and activated CD19(+) cells obtained from human blood. We identified four SNPs (g-1729G>A, g.2295T>C, g.2445G>A and g.2493G>A) and one variation site (g.894delT) in the TNFRSF17 gene using direct sequencing analysis. In addition, the association of the genotype and allelic frequencies of these SNPs was studied in healthy controls and in patients with ulcerative colitis (UC) or irritable bowel syndrome (IBS). Although, the genotype and allelic frequencies of these SNPs, in the UC and IBS patients, were not significantly different from those in the healthy controls, the distribution of the AAG, GGA, AGG and AAA haplotypes, of the SNPs (g.-1729G>A, g.2445G> A and g.2493G>A) associated with the TNFRSF17 gene, in the UC patients, were notably different from those of the healthy controls (P = 0.002, 0.002, 4.7E-4 and 3.3E-6, respectively). Moreover, the frequencies of the AAG, AGG, GAG and GAA haplotypes were significantly different in the IBS patients compared to the healthy controls (P = 4.2E-5, 4.4E-17, 1.8E-22 and 1.6E-10, respectively). These results suggest that the haplotypes of the TNFRSF17 polymorphisms might be associated with UC and IBS susceptibility.