Since the inverse relationship between the levels of apoA-Ⅰ in plasma and the risk of cardiovascular disease is derived from the atherosclerosis (AS). Lipid apoA-Ⅰ formation of high-density lipoprotein(HDL), which by promoting reverse cholesterol transport(RCT) helps cholesterol efflux. α-Helix plays an important role in cholesterol efflux, it’s the acceptor of lipid on apoA-Ⅰ. The mimic peptides of apoA-Ⅰ have similar structure with α-helix, and they can inhibit the development of AS by different ways. This review focuses on the effects of α-helix of apoA-Ⅰ in cholesterol efflux, in order to further explore the structure of apoA-Ⅰ influence on cholesterol efflux, aims at providing the new thought and therapy targeting for AS.