OBJECTIVE: To investigate the perioperative complications and safety of microwave ablation (MA) therapy for patient's non-small cell lung cancer (NSCLC) combined with severe chronic obstructive pulmonary disease (COPD). METHODS: A total of 28 patients with NSCLC combined with severe COPD in our center were analyzed for complications during MA therapy and post-treatment outcomes. RESULTS: All patients were successfully ablated by puncture, with a tumor efficiency of 85.7% and no death within 30 days. The tumor tissues showed hypodense changes, cavitation, and decreased CT values when the CT was reexamined 24 hours after surgery. A total of 24 patients showed different surgery-related complications, and were cured after targeted treatments. During the follow-up, the lung tumor disappeared, while the fibrous scars and foci as well as pulmonary cavity still remained. CT imaging examination showed there was no enhancement in the tissue after resection. CONCLUSION: In this study, we confirmed that the complications of NSCLC combined with severe COPD after MA were manageable, safe and effective.