In recent years, with the advancement of medical, extracorporeal life support technology has become an important strategy for critically ill patients, such as continuous renal replacement therapy (CRRT), extracorporeal membrane oxygenation (ECMO), etc. Effective anticoagulation and less bleeding complications are the main contradictions that need to be solved urgently during extracorporeal life support. Currently, unfractionated heparin remains the most commonly used for anticoagulation. However, hemorrhage associated with systemic heparinization remains a major complication and is directly related to patient outcomes. Various improved anticoagulation techniques have been used to reduce the risk of bleeding. Nafamostat Mesylate (NM) is a synthetic ultra-short-acting serine protease inhibitor, which can play an anticoagulant role by inactivating thrombin and inhibiting the activation of coagulation factors. Evidences show that NM can reduce the incidence of bleeding without increasing the incidence of thromboembolism. We aim to summarize the anticoagulation application of NM in CRRT and ECMO in critically ill patients on the basis of existing literature reports, in order to provide reference for the anticoagulation management during treatment.