Pneumothorax is a rare complication in cancer chemotherapy. We report a case in which a male patient with advanced non-small cell lung cancer (NSCLC) developed repetitive pneumothorax after receiving a combination of the chemotherapeutic drugs gefitinib and amrubicin (GEF + AMR). Both episodes of pneumothorax occurred on the 3rd day of GEF + AMR administration. Tube thoracostomy was performed, but pulmonary air leaks persisted in the second pneumothorax. Whereas surgical intervention was not applicable because of poor respiratory reserve, the chest tube was successfully removed by endoscopic occlusion of bronchopleural fistula with endobronchial Watanabe spigots (EWSs), a type of silicone bronchial blocker.