Background: Standard treatment for patients with locally advanced laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) is total laryngectomy, which seriously affects the quality of life. Neoadjuvant treatment with Nab-paclitaxel plus cisplatin(TP) has favorable efficacy with acceptable toxicity for laryngeal preservation in LHSCC. Programmed death 1 (PD-1) blockade plus chemotherapy has shown a survival benefit and recommended as the first-line treatment in recurrent or metastatic head and neck cancer, but the safety and activity in the combination of TP and PD-1 blockade in locally advanced LHSCC need investigation. Methods: In this single-center, single-arm, phase 2 trial, newly diagnosed pts with stage T3-4N0-3M0 laryngeal SCC or T2-4N0-3M0 hypopharyngeal SCC were recruited. Eligible patients received chemotherapy [Nab-paclitaxel 240 mg/m² plus cisplatin 75 mg/m²] and toripalimab[240 mg, d1]every 3 weeks for 3 cycles. After induction treatment, patients achieving clinical partial response (cPR) or complete response (cCR) received definitive radiotherapy, while those with stable diseases(SD) and progression disease(PD) received surgery plus adjuvant radiotherapy. Toripalimab was given intravenously once every 3 weeks for up to 10 cycles, including 3 cycles before. The primary endpoint was the objective response rate (ORR) according to RECIST 1.1 by investigator assessment to neoadjuvant chemoimmunotherapy. The secondary endpoints included laryngectomy-free survival (LFS), disease failure-free survival (DFS)and overall survival OS at 2 years, quality of life (QOL) and toxic effects. Results: From October 2020 to May 2022，25 patients received neoadjuvant chemoimmunotherapy (median age 58 years; 23.9% men), 52% (13/25) and 48% (12/25) were hypopharyngeal and laryngeal squamous cell carcinoma. 80% (20/25) were clinical T3/4 and 64.0% (16/25) ≥N2. After neoadjuvant chemoimmunotherapy, 2 patients achieved CR, 21 achieved PR, with an ORR of 92%(23/25), 23 patients with CR/PR of the primary tumor received concurrent radiotherapy and immune maintenance therapy, 2 patients with SD/PD received laryngectomy. At a median follow-up of 17 months (range 8-27 months), 1-year DFS was 88.0% , 1-year OS was 96.0% , 1-year LPS was 92.0%, Respectively, only grade 1-2 adverse events occurred in 100% of patients, including loss of appetite (100%), anemia (92.0%), nausea (84.0%), vomiting (52.0%), hypothyroidism (16.0%), peripheral neuritis (20%), leukopenia (12.0%), rash (12.0%). Conclusions: Neoadjuvant treatment with TP plus toripalimab achieved impressive ORR and 1-year LPS rate with manageable toxicities in patients with LHSCC. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: ChiCTR2000033506.