Mitochondrial uncoupling proteins (UCPs) are a subfamily of the mitochondrial transporter family, which locate in the inner mitochondrial membrane. UCPs play a role in transferring proton from membrane space to matrix, reduction of proton gradient and uncoupling the oxidative phosphorylation, which ultimately leads to the decreases of ATP levels in cell. There are 5 members (from UCP1 to UCP5) in total in UCPs family. UCP1 is expressed exclusively in the brown adipose tissue (BAT) and is responsible for non-shivering thermogenesis. UCP2, UCP4 and UCP5 (brain mitochondrial carrier protein 1, BMCP1) were found to be expressed in the brain at high level. Recently, the important roles of UCPs in the pathophysiological process of the hypoxia and ischemia brain diseases have emerged, but these roles are also controversial. Some people think that uncoupling process by UCPs aggravates the energy failure and accelerates the progress of the disease, while others think that UCPs could regulate the mitochondrial membrane potential (MMP), reduce ROS generation and maintain the calcium homeostasis, and thus protect the central nerve system.