AbstractPurposeFurther improvement in clinical outcomes is needed for patients with head and neck squamous cell carcinoma (HNSCC), as there is typically a poor prognosis at diagnosis. This study aimed to report the preliminary therapeutic outcomes and side effects in patients with HNSCC receiving particle beam radiotherapy (PBRT), owing to the physical and biological advantages of this approach.MethodsWe retrospectively analyzed 68 patients with newly diagnosed HNSCC who received PBRT at the Shanghai Proton and Heavy Ion Center (SPHIC) between August 2015 and December 2020. The Kaplan–Meier approach was used to determine overall survival (OS), disease‐specific survival (DSS), progression‐free survival (PFS), local recurrence‐free survival (LRFS), regional recurrence‐free survival (RRFS), and distant metastasis‐free survival (DMFS). Common Terminology Criteria for Adverse Events (CTCAE) 4.03 was also used to grade acute and late toxicities.ResultsWith a median follow‐up time of 24.5 months (range, 3–65), the 3‐year OS, DSS, PFS, LRFS, RRFS, and DMFS rates for the entire cohort were 79.0%, 84.7%, 67.9%, 83.5%, 83.3%, and 96.1%, respectively. Univariate and multivariate analyses showed that N category was a significant predictor of OS, PFS, and RRFS. In terms of acute toxicities, two patients demonstrated severe mucositis or dysphagia, and two patients also displayed a late toxicity of significant mucosal necrosis.ConclusionThese findings suggest that PBRT can provide patients with HNSCC with a promising therapeutic benefit and manageable toxicity. Prospective evaluation of clinical outcomes with PBRT for HNSCC is warranted, with an emphasis on clinical effectiveness as well as adverse effects and patient quality of life.