The tumor necrosis factor and TNF receptor (TNF-TNFR) superfamily plays very important roles in the pathogenesis of many immune-mediated diseases. Regulation of TNF-TNFR superfamily gene expression influences many aspects of the pathology associated with these diseases. In order to investigate genetic variations in the regulatory regions of the TNF-TNFR superfamily genes, promoter regions were screened by sequencing DNA samples from 24 unrelated Korean individuals. We identified a total of 68 single-nucleotide polymorphisms (SNPs) in the regulatory regions of the known TNF-TNFR superfamily genes, including 50 SNPs in the promoter regions, 16 SNPs in the 5'-UTR regions, and two SNPs in the coding regions of these genes. Among the 68 SNPs identified in this study, 25 SNPs were novel SNPs. Interestingly, the sequence alteration created by 11 SNPs completely abolished putative transcription factor binding sites in these alleles. These results suggest that these SNP sites can regulate gene expression by controlling the binding of transcription factors. The identification of function-altering SNPs in the promoter regions of the TNF-TNFR superfamily will facilitate efforts to understand the association of TNF-TNFR superfamily genes with several immune-mediated human diseases.