Background: Many studies have shown that hypertension may contribute to thoracic aortic dissection (TAD). Among the factors that modulate hypertension are endoplasmic reticulum stress and vascular smooth muscle cell proliferation which are in turn modulated by mitofusion-2 (Mfn2). Specifically, we determined, in the Han Chinese population, whether single nucleotide polymorphisms (SNPs) of Mfn2 influenced the occurrence of TAD. Material/Methods: Six tagging SNPs of Mfn2 (rs2236057, rs3766741, rs2236058, rs17037564, rs2295281, and rs2336384) were genotyped using a TaqMan assay in 200 TAD patients and 451 health individuals from the Han Chinese population. Results: Logistic regression analysis indicated CC genotype of rs2295281 was highly linked to an increased risk of TAD (TT+CT versus CC, OR=0.540, 95% CI [0.320-0.911], P=0.021), implying that TT genotype and CT genotype of rs2295281 have a lower risk for TAD. Logistic regression analysis also indicated that rs2236058 was highly linked to the risk of TAD based on recessive genetic model, which indicated that the GG genotype was a protective factor against TAD (GG versus (CG+CC), OR=0.545, 95% CI [0.351-0.845], P=0.007). CG genotype and CC genotype of rs2236058 had a higher risk for TAD. In addition, rs2236058 was linked to the risk of TAD in the recessive genetic and homozygous models in the normotensive subgroup (GG versus (CG+CC), OR=0.298, 95% CI [0.112-0.792], P=0.015; GG versus CC, OR=0.528, 95% CI [0.302-0.925], P=0.026) but not in the hypertension subgroup. Conclusions: Our findings showed that the occurrence of TAD in a Han Chinese population was influenced by Mfn2 polymorphisms.