Cholesterol homeostasis is critical for proper cellular function in the organism. Abnormal accumulation of cholesterol in the body caused by metabolic disorder can lead to hepatic steatosis and hypercholesterolemia, which is closely correlated to cardiac cerebrovascular disease such as arteriosclerosis. The liver plays a key role in maintaining cholesterol homeostasis through regulating its uptake, biosynthesis, conversion, and efflux. This paper reviews the progress in the regulation of cholesterol metabolic homeostasis by the liver.