We investigated the possible association of the functional polymorphisms in the tumor necrosis factor (TNF) genes with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA).The TNF-alpha-308G/A and TNF-beta+252G/A single nucleotide polymorphisms (SNPs) were genotyped using polymerase-chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, in 555 cancer patients (291 ESCC and 264 GCA) and 437 healthy controls in a high incidence region of North China.Among healthy controls, frequencies of the TNF-alpha 1/1, 1/2 and 2/2 genotypes were 89.4%, 9.2% and 1.4% respectively, while frequencies of the TNF-beta B1/B1, B1/B2 and B2/B2 genotypes were 12.6%, 32.3% and 55.1%, respectively. No significant difference was found in the overall genotype and allelotype distribution of the TNF-alpha-308G/A and TNF-beta+252G/A SNPs among cancer patients and controls. However, both the B1/B1 genotype and B1/B2 genotype significantly increased the risk of developing ESCC [the age and gender adjusted odds ratio (OR) = 2.04 and 1.91, 95% confidence interval (CI) = 1.04 - 4.43 and 1.14 - 2.60, respectively] and GCA (the age and gender adjusted OR = 2.68 and 2.64, 95% CI = 1.14 - 6.29 and 1.47 - 4.72, respectively) in individuals with negative family history of UGIC, in comparison with the B2/B2 genotype. When the two TNF polymorphisms were combined and analyzed, individuals with the TNF-beta B1/B2 and TNF-alpha 1/2 or 2/2 genotypes significantly reduced the risk of developing ESCC and GCA, in comparison with those harboring the TNF-beta B2/B2 and TNF-alpha 1/1 genotypes (the age and gender adjusted OR = 0.37 and 0.34, 95% CI = 0.15 - 0.92 and 0.13 - 0.90, respectively).Therefore, the TNF-alpha-308G/A and TNF-beta+252G/A genotyping may be used as a stratification markers to predicate the risk of ESCC and GCA development in North China.