Background: Allergic rhinitis (AR) is a non-infectious chronic inflammatory disease of the nasal mucosa that is mainly mediated by IgE after exposure to allergens. Tumor necrosis factor-alpha has been found to be involved in inflammation response. In the present study, we screened several SNPs of TNF-alpha gene and analyzed the associations between target SNPs polymorphism and AR. Methods: Using an unmatched case-control design, 600 AR patients and 600 healthy controls were enrolled. General characteristics were collected including IgE expression. Univariate and multivariate logistic regression were used to estimate the odds ratio (OR) and 95% confidence interval (CI) of TNF-alpha gene for AR in dominant model, additive model, recessive model and allele model. The haplotype analyses were performed using rs1799964, rs1800630 and rs769178. Stratified analyses were also performed in gender, age, overweight, smoking, drinking, family history, and asthma history. Results: Our multivariate logistic regression indicated that rs1799964, rs1800630 and rs769178 locus polymorphisms are not associated with AR. For rs769178, the GT (OR=2.35, 95% CI:1.82-3.03, P<0.001) and GT+TT (OR=1.89, 95% CI: 1.50-2.38, P<0.001) genotypes present an increased risk for AR compared to GG. The C-G-A-T (OR=2.04, 95% CI: 1.21-3.44, P=0.007) and C-G-C-T (OR=1.29, 95% CI: 1.04-1.62, P=0.024) haplotypes are associated with the increased risk of AR, and the C-G-C-G haplotypes decreased risk of AR (OR=0.75, 95% CI: 0.63-0.88, P=0.001). Stratified analyses shown a significant association between recessive model of rs769178 locus and AR risk in the subgroup of age <= 60, overweight and smoking. Cross-over analysis indicated that the effects of TT+GT of genotype combined with smoking or drinking related with AR were associated with AR risk. Conclusion: The rs769178 locus polymorph of TNF-alpha was associated with an increased risk of AR. The haplotypes (C-G-A-T and C-G-C-T) of TNF-alpha can significantly increase the risk of AR, and C-G-C-G haplotype decreased the risk of AR. There are interactions between rs769178 polymorphism and smoking/drinking for AR risk.