Background: Locally-advanced lung squamous cell carcinoma represents a special subset that is challenging to resect completely with surgery alone. Immunotherapy has achieved great success in treating late-stage lung cancer. However, whether neoadjuvant immunotherapy can facilitate resection of initially locally-advanced and surgically-difficult locally-advanced lung squamous cell carcinoma remains to be investigated. Methods:We retrospectively collected clinical records of locally-advanced lung squamous cell carcinoma patients who received neoadjuvant immunotherapy followed by surgery between 2018 and 2020 at a large academic thoracic cancer center.Results: A total of 23 patients (22 males, 1 female) with locally-advanced locally-advanced lung squamous cell carcinoma were included, initially clinically staged at IIIA (16, 69.6%), IIIB (n=4, 17.4%), IIB (n=2, 8.7%) and IIIC (n=1, 4.3%). The median interval between final treatment to surgery was 36 days (range, 25-93 days), without treatment-related delay in surgery. The neoadjuvant treatment resulted in a high rate of radical resection (n=20, 87.0%). The final histopathological examination demonstrated 6 (26.1%) cases with pathological complete response and 8 (34.8%) with pathological major response. Comparing with the computed tomography scan-based response, we observed a very low consistency (weighted kappa =0.122, P=0.315) between the computed tomography scan-based and final pathological evaluation. The median follow-up time was 510 days (range, 217-920 days). At the end of the follow-up, 1 patient died.Conclusions: Our findings showed the clinical promise of neoadjuvant immunotherapy plus surgery for locally-advanced lung squamous cell carcinoma. Computed tomography scan displays a poor role in assessing the resectability after neoadjuvant immunotherapy.