Objective:To investigate the correlation of the singe nucleotide polymorphisms (SNP) of natural-killer group 2,member D (NKG2D) gene with non-small cell lung cancer (NSCLC) in a Yunnan Han population.Method:TaqMan asssy was used to study genotype 2 SNPs (rs2255336 和 rs2617160) in NKG2D gene in 467 NSCLC patients (including patients in Ⅰ + Ⅱ and Ⅲ + Ⅳ stages,namely group Ⅰ + Ⅱ and group Ⅲ + Ⅳ) and 490 healthy people (control group).The distribution of alleles,genotypes and the constructed haplotypes were analyzed.Results:The allelic and genotypic frequencies of the 2 SNPs were not significantly different between Ⅰ + Ⅱ,and control group,and between 11Ⅲ + Ⅳ and control group (P > 0.05).While results of inheritance mode analysis showed that the best fit inheritance model for rs2255336 and rs2617160 in 2 lung cancer groups was recessive model.The CC-CT genotype of rs2255336(P =0.040,OR =0.26,95% CI:0.06-1.17) and the TT-AT genotype of rs2617160 (P =0.045,OR =0.60,95% CI:0.36-1.00)might be the protective factors against NSCLC development.Conclusions:Polymorphisms (rs2255336 and rs2617160) in NKG2D gene might eorrelate with NSCLC in this Yunnan Han population.