Congenital pulmonary airway malformation (CPAM) is one of the rare developmental lung malformations. Huge cystic lesions are rare and usually characterized by respiratory distress, repeated pulmonary infections and pneumothorax, posing a great threat to the survival of neonates. This article reported the anesthetic management for a neonate who was diagnosed with CPAM and underwent thoracotomy lobectomy. During the surgery, it is necessary to conduct lung isolation, so as to facilitate the exposure of the surgical field and protect the contralateral lung. However, considering the physical characteristics of neonate airway, the strategies for lung isolation are limited. Furthermore, CPAM Neonates also have multiple‑organ malformations, and feature poor surgical tolerance, posing challenge for anesthesiologists.