Epithelioid Hemangioendothelioma (EHE) is an extremely rare malignancy originating from endothelial cells, with an incidence rate of less than 1/100,000. To date, there have been no documented cases of Diaphragm EHE in the English or Chinese literature. EHE can manifest in various organs throughout the body and lacks distinctive clinical features, often leading to misdiagnosis. Given its rarity, there is currently no standardized treatment protocol, management options include radiotherapy, chemotherapy, and targeted therapy. In this report, we present a case study of a 75-year-old male patient who presented with a 6-month history of cough, sputum production, chest tightness, and pleural effusion. A biopsy of the diaphragm mass and immunohistochemical analysis of the pleural fluid confirmed the diagnosis of EHE. The patient underwent chemotherapy combined with targeted therapy, however, unfortunately experienced disease progression. In March 2023, a 75-year-old male patient was admitted to our hospital with persistent cough for over two months accompanied by sputum production and chest tightness. The patient was diagnosed with Diaphragm EHE accompanied by pleural effusion and received treatment at our institution. We initiated combination chemotherapy using albumin-bound paclitaxel and cisplatin along with intrapleural infusion of bevacizumab as an anti-angiogenic drug. After one cycle of treatment, significant control over the pleural effusion was observed which prompted us to administer systemic treatment through intravenous infusion using albumin-bound paclitaxel, cisplatin, and bevacizumab. Unfortunately, the patient's condition continued to deteriorate.When accompanied by pleural effusion, EHE often demonstrates rapid disease progression.© 2024. The Author(s).