Background　Postoperative cognitive dysfunction (POCD) is a significant mental problem after major surgery, but its mechanism remains unclear. For the past few years, multiple evidences support the pathogenic role of neuroinflammation in POCD. Purpose　This article reviews the pathogenic role of central nervous system inflammation in POCD on recent updates. Content　Elderly patients with metabolic syndrome, atherosclerosis and Alzheimer’s disease are more susceptible to POCD. The common factor of these susceptible states is the chronic inflammation. Surgical trauma is not itself considered to be a disease but surgical intervention (the "second hit") lead to the development of a systemic inflammatory state and exaggerate the neuroimmuno-inflammatory response cascade, which does mischief to facilitate POCD. Trend　To control perioperative neuroimmuno-inflammatory response may reduce the morbidity of POCD.