A 56-year-old man attended the emergency room with respiratory failure, deteriorated general status, fatigue, and diarrhea. His clinical history included a liver transplant because of alcoholic cirrhosis, which developed to hepatocellular carcinoma. Initial immunosuppression consisted of corticosteroids, tacrolimus, and mycophenolate mofetil. Examination of the explant revealed vascular invasion, and tacrolimus was replaced with everolimus. The patient presented recurrence of the carcinoma with peritoneal implants, and treatment with sorafenib was started. He was admitted to the gastroenterology department and, after withdrawal of sorafenib, the patient improved clinically. However, 6 days later, he was admitted to the intensive care unit with acute respiratory failure and metabolic acidosis. The final diagnosis was cardiogenic shock. Although cardiogenic shock is not mentioned in the summaries of product characteristics of sorafenib or everolimus, there are reports of a relationship between cardiotoxicity and antiangiogenic therapy that inhibits the proliferation of vascular smooth muscle cells, as is the case with these drugs. We believe that there is a relationship between sorafenib (especially when combined with everolimus) and cardiogenic shock. Application of the Karch and Lasagna algorithm to assess the causality of the reaction induced by the combination of sorafenib and everolimus revealed the relationship to be probable.