Pain is one of the most common symptoms of malignant peritoneal mesothelioma. Therefore, analgesia serves an indispensable role in the treatment of this condition. Morphine is a representative opioid, which is widely used in clinical practice; however, excessive or unreasonable application can cause poisoning. Few cases of morphine poisoning have been reported, and cases of morphine poisoning in patients with malignant peritoneal mesothelioma are even more rare. Here, we present a case of morphine poisoning in a patient with malignant peritoneal mesothelioma. The patient had a high abdominal tumor load, hepatorenal insufficiency, and was treated with a combination of morphine and the sedative benzodiazepine, eventually leading to morphine poisoning. Therefore, for cancer pain, omni-directional and whole-process management should be emphasized. In patients with hepatorenal insufficiency, those treated with morphine combined with benzodiazepines, or those with a high abdominal tumor load, attention should be paid to drug absorption, excretion and interaction, and the drug dose during administration should be reduced to avoid drug poisoning. If poisoning symptoms occur, timely measures should be taken to reduce poison absorption and increase poison excretion, and antagonists should be used to reverse the poisoning and reduce the damage caused.Copyright: © Zhao et al.