We report a case of fatal liver failure associated with gemcitabine hydrochloride(GEM)therapy. In February 2005, a 79-year-old man with a history of diabetes mellitus and chronic hepatitis C was admitted for the treatment of carcinoma of the head of the pancreas. Abdominal CT revealed no distant metastases, but the tumor had invaded the portal vein. Surgery was too risky because of his age and condition, so radiation therapy(60 Gy)was combined with GEM(800 mg on days 1 and 8 of a 3-week cycle). The treatment was well tolerated. During the sixth cycle of GEM, total bilirubin gradually increased to 4.0 mg/dL. Abdominal CT revealed neither dilatation of the bile ducts nor liver metastases, and serology showed no reactivation of hepatitis C. Despite administration of prednisolone(50 mg/day), his liver failure rapidly worsened and he died in October 2005. Autopsy revealed extensive centrilobular necrosis of the liver and confirmed a diagnosis of drug-induced liver failure. The hepatotoxicity of GEM is known, but has usually been described as mild, transient, and rapidly reversible. In patients with chronic liver disease, however, GEM has the potential to cause fatal liver failure. Careful monitoring is necessary during GEM therapy, especially in patients with liver dysfunction.