Aim: This article aims to identify risk factors for severe radiation-induced oral mucositis (RIOM) in head and neck cancer (HNC) patients. In addition, we intend to establish a predictive model in patients undergoing intensity-modulated radiotherapy. Patients & methods: In this retrospective study, several HNC patients (n=179) treated at Zhejiang Provincial People's Hospital from January 2019 to June 2023 were considered. The recruited subjects were divided into modeling and validation groups. The experimental data on clinical characteristics and treatment were collected and analyzed to identify predictive factors for severe RIOM based on the logistic regression approach. Results: The results indicated that severe RIOM occurred in 55.3% of patients. Accordingly, significant predictors included smoking history, diabetes, concurrent chemotherapy, cumulative radiation dose and weight loss of ≥5% in relative to admission weight. A nomogram based on these factors was validated, showing excellent predictive accuracy. Conclusion: In summary, the predictive model could effectively identify high-risk patients for severe RIOM, enabling the design of targeted interventions and improving patient management during radiotherapy.