Objective To evaluate the correlation of the single nucleotide polymorphisms (SNPs) in CDH13 with non-small cell lung cancer (NSCLC) . Methods 115 patients with NSCLC and 110 healthy controls were included in present study. Two SNPs (rs11646213 and rs7195409) in CDH13 were genotyped using TaqMan method. The association of these two SNPs with NSCLC was calculated and assessed. Results The genotypic and allelic frequencies of rs11646213 showed significant difference between NSCLC patients and the control group (P<0.05), (OR=0.464, 95% CI:0.273~0.789) . The genotypic and allelic frequencies of rs7195409 showed significant difference between the stage I+II and stage III+IV groups (P<0.05), (OR=0.491, 95% CI:0.243~0.991) . Conclusions The rs16146213 has a strong association with NSCLC and G allelic showed a protective effect. The rs7195409 has a strong association between stage I+II and III+IV in NSCLC, and G allele may play a protective role in the development of NSCLC.