Abstract: Cystine/glutamate antiportersystem Xc(-) is a sodium independent amino acid transporter, which is a heterodimer composed of light chain subunit xCT and heavy chain subunit 4F2hc (CD98) through covalent disulfide bond. System Xc(-) typically mediates cystine uptake and glutamate output, helps to maintain the balance of glutamate, cystine and cysteine inside and outside the cell, regulates the level of glutamate inside and outside the membrane and the synthesis of intracellular glutathione, thus affecting oxidative stress and glutamate neurotoxicity. This review expounds the structure and function of system Xc(-), analyzes the role of the transporter in physiology and pathology, discusses the role and mechanism in different diseases, and discusses the specific research progress of system Xc(-) as a drug target. This review summarizes the research status of system Xc(-) and provides theoretical guidance for further research on system Xc(-) and drug discovery.