Acute aortic dissection(AAD) is a medical emergency caused by the destruction of the aortic tunica media and is always fatal. Genetic disorders are known to be responsible for AAD, but little is known about the etiology of other non-genetic cases. Tenascin-C(TnC) is a large extracellular matrix glycoprotein and mechanical stretching can up-regulate TnC expression. TnC knockout (TnC-KO) mice have higher blood pressure in the aortic artery and are liable to develop AAD; and mice with AAD have more inflammatory cells in the aortic tissue. TnC prevents aorta from AAD by regulating ECM structure, regulating vascular smooth muscle cell function and inhibiting inflammatory response in the aorta. In this paper we reviewed the role of TnC in the development and progression of AAD.