Postoperative exacerbation of interstitial pneumonia in patients with lung cancer and interstitial lung disease has emerged as a serious problem. Therefore, the risk factors for postoperative exacerbation of interstitial pneumonia in patients with interstitial lung disease must be identified. We analyzed 22 patients diagnosed as having lung cancer with interstitial lung disease who underwent surgical treatment at the Kitasato University Hospital. Among the patients with lung cancer and interstitial lung disease, 5 patients (22.7%) had postoperative exacerbation of interstitial pneumonia. The prognosis of the patients with postoperative exacerbation was significantly poorer than that of patients without. Patients with postoperative exacerbation had a significantly higher age (≥75 years) and a significantly lower frequency of postoperative administration of steroid than patients without postoperative exacerbation. Almost all patients with postoperative exacerbation underwent lobectomy, had elevated KL-6 levels in the serum pre-operatively, and had significantly advanced stages of disease. Of the 5 patients with postoperative exacerbation, 2 had a history of inflammation prior to their exacerbation: 1 had a common cold and the other pyothorax. In patients with lung cancer and interstitial lung disease, advanced age, advanced stage disease, no postoperative administration of steroid and a pre-operative episode of inflammation are all risk factors for postoperative exacerbation of interstitial pneumonia.