biostudies-literatureFan LChinese National Natural Science Foundation1895https://www.ebi.ac.uk/biostudies/studies/S-EPMC12528569biostudies-literatureUnknown16(1)<h4>Background</h4>Head and Neck Squamous Cell Carcinoma (HNSCC) is an aggressive malignancy with poor prognosis and low five-year survival rates. Ferroptosis, an iron-dependent form of cell death, has emerged as a potential factor in cancer therapy. This study aimed to identify differentially expressed genes (DEGs) associated with HNSCC, ferroptosis, and radiotherapy, and to develop a diagnostic model to establish novel biomarkers, early diagnosis and individualized therapy.<h4>Methods</h4>We analyzed TCGA-HNSCC, GSE6631, and GSE107591 datasets to identify Ferroptosis- and Radiotherapy-Related Differentially Expressed Genes (F&RRDEGs).Ferroptosis & radiotherapy scores were calculated, followed by immune infiltration and immunotherapy analyses. A Cox prognostic model was evaluated using noDiscover oncologyFerroptosis and radiotherapy-related genes in head and neck squamous cell carcinoma: diagnostic and prognostic significance.PMC1252856982071168Shi LMu YFan LWang ZWang JfalseFerroptosis and radiotherapy-related genes in head and neck squamous cell carcinoma: diagnostic and prognostic significance.<h4>Background</h4>Head and Neck Squamous Cell Carcinoma (HNSCC) is an aggressive malignancy with poor prognosis and low five-year survival rates. Ferroptosis, an iron-dependent form of cell death, has emerged as a potential factor in cancer therapy. This study aimed to identify differentially expressed genes (DEGs) associated with HNSCC, ferroptosis, and radiotherapy, and to develop a diagnostic model to establish novel biomarkers, early diagnosis and individualized therapy.<h4>Methods</h4>We analyzed TCGA-HNSCC, GSE6631, and GSE107591 datasets to identify Ferroptosis- and Radiotherapy-Related Differentially Expressed Genes (F&RRDEGs).Ferroptosis & radiotherapy scores were calculated, followed by immune infiltration and immunotherapy analyses. A Cox prognostic model was evaluated using no2025-01-01T00:00:00Z2025 Oct2026-07-15T14:37:20.39Z2026-07-06T03:08:43.48ZS-EPMC125285694109134210.1007/s12672-025-03713-7