Aortic dissection (AD) is a disease characterized by a tear in the aortic intimal layer and separation of the arterial wall. Some risk factors, such as hypertension and Marfan syndrome, are well known in AD, but the role of genetic factor is largely unknown. In this study, we investigated the relation between two single nucleotide polymorphisms (SNPs) identified by genome-wide association study and AD. Approximately 177 patients diagnosed with AD through clinical evaluation and imaging techniques and 183 age- and sex-matched control subjects who were suffering from chest pain but without AD were included in the study. Genotyping of rs10263935 and rs6045676 was performed in both patients and control subjects using the TaqMan® method [Life Technologies (AB & Invitrogen), Carlsbad, CA]. The frequency of the AA and AG genotype in rs10263935 was significantly higher in the AD patients (0.085 and 0.435, respectively) than in the control subjects (0.033 and 0.355, respectively). The rs10263935 A allele frequency in the AD patients was higher than that in the control subjects [0.302 vs 0.210, odds ratio (OR) = 1.62, 95% confidence interval (CI): 1.26–2.28, P = 0.005]. Similarly, the frequency of the GG genotype in rs6045676 was significantly higher in the AD patients than in the control subjects (0.107 vs 0.038, P = 0.015). The rs6045676 G allele frequency in the AD patients was higher than that in the control subjects (0.282 vs 0.191, OR = 1.67, 95% CI: 1.18–2.50, P = 0.004). After adjustment of the confounding factors, such as smoking, sex, and age, the differences remain significant in several models (rs10263935: GG vs AA: OR = 3.13, 95% CI: 1.15–8.33, P = 0.025; GG vs AG: OR = 1.57, 95% CI: 1.01–2.44, P = 0.045; rs6045676: GG vs CC: OR = 3.30, 95% CI: 1.32–8.25, P = 0.011). rs10263935 on chromosome 7 and rs6045676 on chromosome 20 are associated with AD. Further studies are warranted to elucidate the functional role of these two variants.