A 71-year-old man without asbestos exposure presented with symptoms of recurrent diarrhea for more than a year, abdominal distension for more than 10 days, and unintentional weight loss of 5 kg over 3 months. Physical examination revealed a 20 cm solid abdominal mass. Abdominal contrast-enhanced CT showed omental-peritoneal “cake-like” thickening with massive peritoneal effusion. Laparoscopic palliative tumor resection and effusion drainage were performed. Postoperative pathology and immunohistochemistry (CK+, CR+, CK5/6+, D2-40+, WT1+, CD20-, CDX2-) confirmed epithelioid mesothelioma of the greater omentum. Postoperative management included anti-infective therapy, nutritional support, and Cinobufacini Capsule-based antitumor therapy. After a 3-month follow-up, the disease was stably controlled. Definitive diagnosis relies on pathology and immunohistochemistry; palliative surgery with adjuvant therapy may yield favorable short-term results.