Abstract： Objective To evaluate the association between the genetic polymorphisms of endoplasmic reticulum aminopeptidase 2 (ERAP2) and the susceptibility of non-small cell lung cancer (NSCLC) in Yunnan Han population.Methods A total of 223 patients with NSCLC and 205 healthy controls in Yunnan Han population were included in the present study.The SNP of rs2248374 and rs2549782 in ERAP2 gene were genotyped using TaqMan fluorescence probe technique,and their haplotypes were constructed.Then,the association between the two SNPs with NSCLC was assessed.Results The allele A and allele G frequencies for rs2248374 in NSCLC patients and the control groups were 45.5％ (203/446),54.5 ％ (243/446) and 37.8％ (155/410),62.2％ (255/410),respectively (x2 =5.220,P ＜ 0.05).The genotypic GG,GT,TT for rs2549782 in NSCLC patients and the control groups were 21.5％ (48/223),48.9％ (109/223),29.6％ (66/223) and 11.7％ (24/205),49.8％ (102/205),38.5％ (79/205),respectively(x2 =8.656,P ＜ 0.05).And the allele G and allele T frequencies for rs2549782 in NSCLC patients and the control groups were 46.0％ (205/446),54.0％ (241/446) and 36.6％ (150/410),63.4％ (260/410),respectively (x2 =7.741,P ＜ 0.05).The frequencies of haplotype rs2248374/rs2549782-AG were 44.6％ (199/446),36.1％ (148/410) and rs2248374/rs2549782-GT were 53.1％ (237/446),61.7％ (253/410),which also showed difference between NSCLC patients and the control groups (x2 =6.567,P ＜0.01 ;x2 =6.567,P ＜0.01).The allele A and allele G frequencies for rs2248374 were 52.9％ (72/136),47.1％ (64/136) and 42.3％ (131/310),57.7％ (179/310) in the Cigarette-smoking group and the Non-smoking group,respectively (x2 =4.498,P ＜ 0.05),while the allele G and allele T frequencies for rs2549782 were 54.4％ (74/136),45.6％ (62/136) and 42.3％ (131/310),57.7％ (179/310) in the Cigarette-smoking group and the Non-smoking group,respectively (x2 =5.831,P ＜ 0.05).The genotypic AA,AG,GG for rs2248374 were 17.3％ (24/139),56.1％ (78/139),26.6％ (37/139) and 27.8％ (22/79),38.0％ (30/79),34.2％ (27/79) in lung squamous cell carcinoma and lung adenocarcinoma,respectively (x2 =6.999,P ＜ 0.05),while the genotypic GG,GT,TT for rs2549782 were 18.7 ％ (26/139),55.4％ (77/139),25.9％ (36/139) and 27.8％ (22/79),36.7％ (29/79),35.4％ (28/79) in lung squamous cell carcinoma and lung adenocarcinoma,respectively (x2 =7.093,P ＜ 0.05).Conclusion ERAP2 rs2248374 and rs2549782 had a strong association with NSCLC and the pathological pattern.The rs2248374/rs2549782-AG haplotype was associated with increased NSCLC risk (OR =1.435,95％ CI:1.088-1.893),whereas the rs2248374/rs2549782-GT haplotype individuals may have a reduced NSCLC risk (OR =0.697,95％ CI:0.528-0.919).