Immune checkpoint inhibitors have brought long-term survival benefit in advanced non-small cell lung cancer patients without driver gene mutations. Even after withdrawal of immunotherapy for a maximum of two years, some patients still benefit from this therapy and the reason is not fully clear. Results from several neoadjuvant trials indicated that in resectable lung cancer patients, neoadjuvant immunotherapy or chemo-immunotherapy led to major or complete pathological responses in a high proportion of tumors. Here we report a case of a brain-metastatic lung squamous cell carcinoma patient who received supratentorial tumor resection and thoracic surgery after chemo-immunotherapy, and achieved a pathological complete response (pCR) in both lesions. This case indicated that pCR can also happen in advanced-stage lung cancer patients receiving chemo-immunotherapy, which may be the reason for long-term benefit of those patients.