Introduction: Tonsillar Squamous Cell Carcinoma (TSCC) is a common, difficult-to-treat oropharyngeal cancer. Case summary: A 50-year-old man was diagnosed with left TSCC with multiple lymph node metastases on the left side of the neck (stage cT3N3b). The patient tested positive for human papillomavirus/p16. Discussion: The patient had a high tumor mutational burden of 14.08 Muts/Mb and positive programmed cell death-ligand 1 expression (15%). A combination therapy of pembrolizumab, docetaxel, cisplatin, and proton and heavy ion therapy was administered. Magnetic resonance imaging after four cycles showed that the left tonsil carcinoma disappeared, and the left cervical lymph node significantly shrank to 1.1 cm, suggesting that the patient achieved a clinical complete response with no signs of disease progression. The patient was administered pembrolizumab every month to maintain for 2 years and followups at the interval of 3 months. The long-term complete clinical response in our case may represent a new combined therapeutic approach for locally advanced unresectable head and neck squamous cell carcinoma.