A tumor was found in the left S10 in a chest CT scan of a 72-year-old male patient with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP). He underwent left lower lobectomy and resection of the hilar and mediastinal lymph nodes under video-assisted thoracoscopic surgery. The histopathological evaluation disclosed a well-differentiated squamous cell carcinoma (T1N0M0; stage IA) associated with UIP. On the sixth postoperative day, a severe hypoxemia (PaO₂ 48 mmHg) developed, and the chest CT showed diffuse ground glass opacity (GGO) in the right lung. A diagnosis of acute exacerbation of IPF/UIP was made, and steroid pulse therapy with cyclosporin A was started. However, despite this therapy, the diffuse GGO extended to both lung fields, and the patient died of respiratory failure 82 days later. The histopathology at autopsy demonstrated diffuse alveolar damage due to UIP that was consistent with acute exacerbation of IPF/UIP. It is suggested that the acute exacerbation of IPF/UIP could have been triggered by a high concentration of oxygen or mechanical lung injury during the patient's surgery.