Background: Although immune checkpoint inhibitors (ICI) have shown promising results, they are worried to use in patients with interstitial lung disease (ILD) because of high risk of complications. The aim of this study was to investigate safety of ICI in lung cancer patients with ILD. Methods: A total of 506 lung cancer patients who were treated with ICI from January 2016 to December 2018 was screened, and clinical data and chest computed tomography (CT) images were retrospectively analyzed. The existence of ILD in these patients was confirmed by chest CT images at the time of lung cancer diagnosis. Results: The median follow-up period after treatment with ICIs was 5 months (interquartile range [IQR], 1-10 months). Among the total subjects, 23 (4.5%) patients had ILD (10 unclassified idiopathic interstitial pneumonia, 6 idiopathic pulmonary fibrosis, 6 interstitial lung abnormality and 1 connective tissue disease related ILD). The mean age of the ILD group was 68.0 years, and 91.3% were male. Among ICI used, nivolumab was the most common (47.8%), followed by pembrolizumab (43.5%) and atezolizumab (8.7%), and the median number of treatment cycle was 4. Drug-related pneumonitis occurred in 8 patients (34.8%) among the ILD group, and it was more frequent than that in the non-ILD group (n=483, 7.7%, P < 0.001). The median duration from start of treatment to pneumonitis was 1 months (IQR, 0-6 months). Among ILD patients with pneumonitis, half of them died due to pneumonitis. ILD patients with drug-related pneumonitis showed numerically shorter survival period (median: 3 vs. 7 months, log rank test P = 0.534, figure 1), compared to those without pneumonitis. Conclusions: One-third of lung cancer patients with ILD treated with ICI experienced drug-related pneumonitis, which caused half of them to die. ICI treatment should be used with caution in lung cancer patients with ILD.