Abstract Background The purpose of this study is to investigate the clinical effectiveness of staging radioactive particle implantation guided by computed tomography (CT) and fiber–optic bronchoscopy in treating cancerous large airway stenosis. Methods A total of 102 patients were included; 57 had undergone staging radioactive particle implantation guided by CT and fiber bronchoscopy and 45 did not. Patients were evaluated by CT and fiber–optic bronchoscopy to determine the feasibility of the implantation of radioactive seeds for the treatment of cancerous large airway stenosis. The treatment planning system (TPS) was used to plan the doses. Radioactive seeds were implanted using fiber–optic bronchoscopy. One week later, CT-guided implantation of radioactive seeds was performed. Results The clinical evaluation showed complete, partial, slight, and non-response in 38, 14, 5, and 0 patients, respectively. None of the patients were found with serious complications. The diameter of the affected airway, Karnofsky score, dyspnea index, survival, and quality of life of the patients in both groups was significantly higher and significantly different after the treatment (P < 0.05). The dyspnea index was significantly lower in the treatment group as compared with the control group (P < 0.001). Conclusion CT- and fiber bronchoscopy-guided staging radioactive particle implantation has definite treatment effectiveness in treating cancerous large airway stenosis. It should be widely used in clinical practices.