We examined the relationship between the NcoI RFLP of tumor necrosis factor beta (TNFB) and alpha (TNFA) genes and the risk of colorectal cancer. The first intron of TNFB and the -308 promoter region of TNFA NcoI RFLP were ascertained from peripheral leucocytes of 136 colorectal cancer patients and 325 healthy controls. The TNFB*1/TNFB*1 homozygote was significantly predominant in patients with colorectal cancer (18.4%) compared to control subjects (9.8%) (p < 0.01), whereas there was inverse association in TNFB*2/TNFB*2. However, the association between colorectal cancer and TNFA genotypes was not found which indicates that these alleles did not appear to be a susceptibility factor for colorectal cancer. TNFB polymorphism was not associated with a clinicopathological parameter of colorectal cancer. However, in regard to the degree of recurrence during the postoperative survival period, TNFB*1/TNFB*1 (12.5%) and TNFB*1/TNFB*2 (24%) were higher than TNFB*2/TNFB*2 (8.3%). Based on these results, it indicates that TNFB*1/TNFB*1 genotypes show an increased risk for colorectal cancer, and that the TNFB*1 allele (R.R. = 1.41) mediates some role in the initial step of tumorigenesis or activation of dormant tumor cells, whereas TNFB*2 allele mediates some functions associated with cytotoxicity of tumor cells.