The tumor necrosis factor-alpha (TNF) and lymphotoxin-alpha (LTA) are proinflammatory cytokines with immunoregulatory effects. TNF is also known to inhibit gastric acid secretion. Previously we have shown that the known proinflammatory genotypes, IL-1B -31C/+ and IL-1RN *2/*2, were not associated with increased risks for gastric cancer/duodenal ulcer in the Korean population. In this study, we tested the association between the polymorphisms of another candidate cytokine TNF/LTA and 341 gastric cancers, 133 duodenal ulcers, and 261 healthy controls. Five TNF promoter polymorphisms (-1031, -863, -857, -308, and -238) and two LTA polymorphisms (intron 1 and Thr26Asn) were analyzed. Individual polymorphisms were not associated with the gastric cancer and/or duodenal ulcer risk. When a haplotype analysis was performed with seven polymorphisms, differences in haplotype profile between the controls and gastric cancer and/or duodenal ulcer were not statistically significant. However, the frequencies of individual haplotypes C and D, which had opposite alleles at -1031, -863, and -857, showed statistically significant differences between the gastric cancer and duodenal ulcer (P=0.005 and P=0.02, respectively), suggesting that the TNF/LTA genotypes might play an opposite role in the pathogenesis of gastric cancer and duodenal ulcer.