This study retrospectively analyzed the curative effect of neoadjuvant PD-1 inhibitors combined with chemotherapy of locally advanced laryngeal and hypopharyngeal cancer and compared with chemotherapy plus EGFR inhibitors and chemotherapy alone. From January 1 2018 to October 1 2023, a total of 113 patients in Beijing Tongren Hospital, who were diagnosed with locally advanced laryngeal cancer and hypopharyngeal cancer and received neoadjuvant immunochemotherapy, were enrolled. The primary outcome measures included objective response rate, organ-preservation rate, downstaging rate, and overall survival. Of 113 patients, including 34 patients were given immunochemotherapy, 38 patients chemotherapy plus EGFR inhibitor, and 41 patients chemotherapy. Most were male, and the median follow-up time in the immunochemotherapy group was 12 months. Neoadjuvant immunochemotherapy could improve the objective response rate (88.2%, p < 0.05), downstaging rate (79.41%, p < 0.05), and organ-preservation rate (97.1%, p < 0.05). However, compared with chemotherapy and chemotherapy plus EGFR inhibitors, immunochemotherapy did not significantly improve patients' 1-year and 2-year survival rates. Neoadjuvant PD-1 inhibitor combined with chemotherapy could improve the objective response rate, downstaging rate, and organ-preservation rate in patients with locally advanced laryngeal and hypopharyngeal cancer. Our study showed that this treatment regimen could more effectively protect the laryngeal function of patients. It provided a new treatment mode for patients with a strong desire to preserve the larynx. Further prospective studies are needed to confirm this conclusion.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.