Recent efforts have been directed toward new therapeutic options to approach drug-induced hepatitis. We report a case of acute liver failure associated with Nimesulide in a 67-year-old man, with a medical history of chronic alcohol abuse. The biopsy was compatible with chronic alcoholic liver disease and acute drug-induced injury. The patient was enrolled to receive G-CSF followed by apheresis and selection of peripheral-blood stem cells. After ultrasound-guided injection of CD34+cells in the portal vein, we observed a rapid improvement of synthetic liver function, with particular reference to coagulation parameters. Liver biopsy performed 20 days after, showed wide areas of regeneration. In the next 30 days the laboratory signs of acute decompensation progressively improved. Unfortunately he died of multiple-organ failure related to bacterial infection. Intrahepatic injection of peripheral-blood stem cells seemed safe and produced good periprocedural results with improvement of synthetic profile, suggesting a possible role of stem cells in the regeneration process.