Background 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). Methods The TNF-α-308G/A and TNF-β+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. Results Among healthy controls, frequencies of the TNF-α 1/1, 1/2 and 2/2 genotypes were 89.4%,9.2% and 1.4% respectively, while frequencies of the TNF-β 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-α-308G/A and TNF-β+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-β B1/B2 and TNF-α1/2 or 2/2 genotypes significantly reduced the risk of developing ESCC and GCA, in comparison with those harboring the TNF-β B2/B2 and TNF-α 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).Conclusions Therefore, the TNF-α-308G/A and TNF-β+252G/A genotyping may be used as a stratification markers to predicate the risk of ESCC and GCA development in North China. Background 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). Methods The TNF-α-308G / A and TNF-β + 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. Results Among healthy controls, frequencies of the TNF-α 1/1, 1/2 and 2/2 genotypes were 89.4%, 9.2% and 1.4% respectively while frequencies of the TNF-β B1 / B1, B1 / No significant difference was found in the overall genotype and allelotype distribution of the TNF-α-308G / A and TNF-β + 252G / A SNPs among cancer patients and controls. However, both the B1 / B1 genotype and B1 / B2 genotype significant ly 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] Bl / 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 and gender adjusted OR = 0.37 and 0.34, 95% CI = 0.15-0.92 and 0.13-0.90, respectively) .Conclusions Therefore, the TNF-α-308G / A and TNF- β + 252G / A genotyping may be used as a stratification markers to predicate the risk of ESCC and GCA development in North China.