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More than 650,000 new cases of head and neck cancer are diagnosed worldwide each year, and approximately half of these patients ultimately succumb to the disease. Head and neck squamous cell carcinoma (HNSCC) accounts for over 90% of all head and neck malignancies, arising from the squamous epithelial tissues of the oral cavity, pharynx, and larynx. The incidence of HNSCC exhibits prominent geographical disparities, with tobacco exposure, alcohol consumption, and human papillomavirus (HPV) infection serving as its major risk factors. Tumor organoids are capable of recapitulating the three-dimensional spatial architecture of primary tumors, stably retaining patient-specific genomic mutations and gene expression profiles, and preserving the core biological features of tumors during long-term in vitro passaging. Compared with patient-derived xenograft (PDX) models, HNSCC organoids achieve a markedly higher success rate of establishment. Furthermore, their morphological and histological characteristics are highly consistent with those of parental tumors, enabling faithful recapitulation of patients’ drug response profiles. Therefore, HNSCC organoids possess broad application prospects in the research of individualized precision cancer therapy.