Statins are mainly used to reduce the content of low-density lipoprotein-cholesterol (LDL-C) and to prevent cardiovascular disease, but its clinical efficacy and the tolerance of body are still uncertain. Human proprotein convertase subtilisin/kexin type 9 (PCSK9), a member of pre-protein convertase family, is mainly produced in the liver and then released into blood, and plays an important role in regulating plasma LDL-C levels by promoting the degradation of low-density lipoprotein receptor (LDLR) in the liver. Both gain-of-function-and loss-of-function-mutation of PCSK9 have great impact on circulating LDL-C levels and the risk of cardiovascular diseases. Statins can up-regulate the expression of PCSK9 through negative feedback regulation by decreasing hepatic cholesterol. As a result, PCSK9 can reduce the efficiency of statins by promoting the degradation of LDLR; therefore inhibiting PCSK9 is expected to be an effective treatment for hypercholesterolemia. In this paper we reviewed the function of PCSK9 in cholesterol metabolism and its clinical application.