Background: Induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) is the standard of care for locally advanced hypopharyngeal squamous cell carcinoma (LA HPSCC). We aimed to assess whether add immunotherapy to ICT further improving patient outcomes. Methods: In this phase II, single-arm study, eligible pts aged 18-70 yrs diagnosed with stage III-IVB (AJCC 8^th) HPSCC received induction therapy with tislelizumab (200 mg), cisplatin (75 mg/m²) and nab-paclitaxel (260 mg/m²) Q3W for 3 cycles. After assessment by multidisciplinary team, pts received surgery or CRT. The primary endpoint was objective response rate (ORR). Secondary endpoints include major pathologic response (MPR) in surgery group, disease control rate (DCR), 2-yr PFS rate in CRT group and 2-yr DFS rate. Results: 29 pts were enrolled (median age, 61 y; 97% male; stage III/IVA/IVB, 7%/90%/3%) from May to Nov 2022. Median follow-up was 7.3 months, no disease progression occurred in all patients. For all pts, the post-induction ORR and DCR were 82% and 100%. In surgery group (n = 10), all pts achieved R0 resection, and 5 (50%) pts reached pathological complete response (pCR). A patient with stable disease underwent a total laryngectomy achieved pCR by postoperative pathologic evaluation. Grade 3 and 4 treatment-related adverse event (TRAE) reached 82.8%, and mainly come from chemotherapy-related neutropenia. There was no TRAE leading to treatment discontinuation. Conclusions: These early data suggested that tislelizumab plus chemotherapy as induction treatment followed by chemoradiotherapy or surgery was safe and had the potential to provide clinical benefits for patients in LA HPSCC. The inconsistency between radiographic and pathological evaluation needs further exploration. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: ChiCTR2200060094.