Spontaneous rupture is a rare and dramatic complication of hepatocellular carcinoma (HCC), burdened by a high mortality. Here we describe a case of a 73-year-old man, who arrived at the ER because of syncope, and acute epigastric and right upper quadrant abdominal pain. He had a history of hepatitis C-related liver cirrhosis and HCC in treatment with sorafenib. The physical examination showed a state of hemorrhagic anemia with the presence of blood in the peritoneal cavity. The patient underwent an urgent liver resection. Thirty days after surgery, he was in good general condition. Sorafenib is a multikinase inhibitor recently introduced in the therapy of patients with advanced HCC. Among the various side effects reported in patients treated with sorafenib, there is a higher risk of bleeding. In conclusion, sorafenib may increase the risk of bleeding and rupture of HCC in susceptible individuals., Ferdinando Rombolà, Angelo Caravetta, Francesco Mollo, Antonio Spinoso, Lenino Peluso, Raffaele Guarino, and Literatura 15