A case of iatrogenic sclerosing cholangitis secondary to hepatic intra-arterial 5-fluorouracil (5FU) and Mitomycin C (MMC) chemotherapy is described. When any unexplained elevation of liver function results in alkaline phosphatase and bilirubin level, chemotherapy should be discontinued, and further examination carried out using ultrasonography, transhepatic cholangiography and endoscopic retrograde cholangio-pancreatography (ERCP). Although percutaneous transhepatic biliary drainage has been effective in some cases, in our case, the clinical course was irreversible and the patient died of hepatic failure and gastrointestinal bleeding. When clinical signs of hepatic dysfunction occur in the absence of tumor progression, iatrogenic sclerosing cholangitis must be suspected.