Ingestion of Amanita phalloides, a deadly wild mushroom, can cause multi-organic injury. The value of therapeutic plasma exchange (TPE) in treating mushroom poisoning was controversial, especially for those patients at the later stage. We reported three cases of acute liver injury, coagulopathy, and hepatic encephalopathy secondary to mushroom poisoning at the later stage. Therapeutic plasma exchange (TPE) session was repeated 2~5 times depending on the patients’ conditions. Pathological plasma ranging from 1600 to 1800 mL was exchanged for each session with fresh frozen plasma and normal saline based on the patients’ body weight. Patients’ liver function, coagulation function, and clinical symptoms were immediately improved upon TPE treatment. TPE is a reliable therapy for patients with acute liver injury, coagulopathy, and hepatic encephalopathy secondary to mushroom poisoning at the later stage of poisoning.