Malignant pleural mesothelioma is a rare tumour with survival of 9-17 months after diagnosis. Radical surgical resection by extra-pleural pneumonectomy combined with hyperthermic intrathoracic chemotherapy has shown to improve patient survival and better microscopic tumour control. Anaesthetic management of this procedure is challenging due to the complex pathophysiological changes associated with prolonged duration of surgery, one- lung ventilation, haemodynamic instability due to major blood loss, temperature variations including heat loss during pneumonectomy and rapid rise in temperature during hyperthermic chemotherapy, cardiac arrhythmias due to exposure to heated chemotherapeutics, cisplatin toxicity and acid-base changes. Intra-operative management involves protective ventilation, regulation of temperature and haemodynamics along with prevention of complications associated with ′heated chemotherapeutics′. Thorough pre-operative assessment and preparation, advanced intra-operative monitoring with prompt corrective interventions, will help in improved patient outcome in the immediate post-operative period. We present one such case done for the 1 st time in India.