A variety of options have been proposed to treat malignant ascites but most of them have failed to reach a significant impact in terms of palliation. Laparoscopic hyperthermic intraperitoneal chemotherapy (LHIPEC) could represent a good therapeutic tool for patients in whom medical therapies have failed and peritoneovenous shunting is contraindicated. Here we present a case of a 49-year-old woman with malignant ascites secondary to peritoneal spreading of a right pleural mesothelioma. After failure of medical therapy, the patient underwent LHIPEC with Cisplatin 25 mg/m2/L and Doxorubicin 7 mg/m2/L. A dramatic reduction of ascites was documented in the postoperative period and the patient experienced complete abdominal symptom relief. Ascites did not recur during a follow-up period of 6 months. LHIPEC could be a good therapeutic option to palliate malignant ascites from mesothelioma in cases not eligible for a radical treatment. Further studies are needed to standardize dosage and perfusion parameters.