Background: Nasal NK/T-cell lymphoma is a rare type of lymphoma in Caucasian individuals, but is relatively common in Asian populations. Genetic variants in immune and inflammatory response genes may thus be associated with the risk of developing lymphoma. Here, we investigated the association between immuno-modulatory gene polymorphisms and risk for nasal NK/T-cell lymphoma in a Chinese population., Methods: Analysis of 12 single nucleotide polymorphisms (SNPs) in IL-10, TNF-α, lymphotoxin-α (LTA), and CTLA-4 genes was performed for 125 patients with NK/T-cell lymphoma and 300 healthy controls by PCR-ligase detection reactions., Results: The LTA +252 GA + AA genotypes were associated with increased risk for NK/T-cell lymphoma (OR = 2.96, 95 % CI = 1.42-6.19, P = 0.004 for GA + AA genotype). Haplotype C-G-G-A (TNF-α -857, -308, -238 and LTA +252) also conferred an increased risk (OR = 1.52, 95% CI = 1.14-2.06, P = 0.005). Additionally, the LTA +252 GA + AA genotype was associated with an even higher risk in populations positive for Epstein-Barr virus (OR = 5.20, 95% CI = 1.22-23.41, P = 0.03 for the GA + AA genotype)., Conclusions: Our data suggest that the LTA +252 A > G polymorphism is associated with the risk of developing NK/T-cell lymphoma, especially for Epstein-Barr virus-positive NK/T-cell lymphoma in the Chinese population.