The hypoxia inducible factor-1α (HIF-1α) is a major regulator of the cellular response to hypoxia, and its high expression is induced in the hypoxic environment of atherosclerosis (As) plaques. It is a key protein to promote the progression of As and widely involved in the occurrence and development of As. This article reviews the structure and function of HIF-1α and its role in endothelial cells, vascular smooth muscle cells, mononuclear macrophages and the differentiation of CD4＋T cells, in order to provide new ideas for the prevention and treatment of As based on HIF-1α.