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Heat stroke is a hyperthermia-induced systemic inflammatory response which may cause multiorgan dysfunction syndrome. We report a case of exertional heat stroke with acute hepatic failure in an 11-year-old boy. He initially presented hyperthermia and unconsciousness, which occurred after heavy exercise. His neurological state improved after terminating the hyperthermia by intensive cooling therapy. However, 24 hours after the initial recovery, his neurological state deteriorated again as acute hepatic injury progressed rapidly. We applied 4 times of total plasma exchange as an immunotherapy for systemic inflammatory response syndrome and acute hepatic failure expecting it to remove endogenous inflammatory factors and hepatotoxic cytokines. Following the plasma exchange, his mental state became normal and serial laboratory findings indicated improvement. He made a complete recovery without sequelae. We experienced successful treatment regarding exertional heat stroke with acute hepatic failure using plasma exchange.