We report a case of serious complications following computed tomography (CT)-guided radiofrequency ablation (RFA) performed for the treatment of lung cancer with interstitial pneumonia. The patient developed delayed-onset pyopneumothorax, which required 6 months of antibiotic treatment, drainage, and video-assisted thoracoscopic debridement. Although CT-guided RFA is a promising, effective procedure for difficult-to-treat lung cancer, the present case suggests a risk of complications for patients complicated with interstitial pneumonia and warrants caution.