The combined modality treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has gained worldwide acceptance for management of selected patients with peritoneal metastases from various cancers. Cytoreductive surgery is performed with the goal of removing all macroscopic disease and is coupled with perioperative chemotherapy (POC) in the form of HIPEC with or without EPIC (early postoperative intraperitoneal chemotherapy) to deal with the microscopic residual disease. These treatments entail the use of cytotoxic drugs in the operation theatre or in the intensive care unit where they are not commonly used and put the healthcare workers participating in the treatment at risk of exposure. CRS is performed with high voltage electrocautery generating a large amount of surgical smoke which is inhaled by the involved personnel and has potential health hazards. This article outlines the safety measures to be taken while performing CRS and POC.