The scavenger receptor class B type I (SR-BI) is a multi-ligand membrane protein receptor that binds to high-density lipoprotein (HDL) under physiological conditions, promoting the selective uptake of cholesterol esters from HDL into cells. SR-BI also promotes the reverse transport of excess cholesterol from peripheral tissues to the liver, contributing to the synthesis of bile acids for excretion and the removal of excess cholesterol from the body, thereby lowering the cholesterol load and exerting anti-atherosclerotic effects. Studies in mice and humans have demonstrated that a functional defect of SR-BI can cause atherosclerotic lesions and cardiovascular diseases, such as myocardial infarction and stroke. Additionally, SR-BI in vascular endothelial cells promoted the deposition of low-density lipoprotein under the endothelium. Although SR-BI is widely expressed in various tissues and cell types throughout the body, its expression level and function vary accordingly. The present review focuses on the biological functions and mechanisms of SR-BI in regulating atherosclerosis.