Background Evidence supporting predictive effects of pretreatment nutritional risk and nutritional status on nutrition impact symptom (NIS) clusters during radiotherapy in patients with head and neck cancer (HNC) is insufficient. Methods At baseline (T1), we collected severity and interference of NIS (Head and Neck Patient Symptom Checklist), nutritional risk, and nutritional status. During (T2) and at the end of radiotherapy (T3), we re‐evaluated NIS. Symptom clusters were identified by exploratory factor analysis using mean scores of NIS severity at T2 and T3. Predictive effects were explored by generalized estimating equations. Results Five hundred thirty‐seven patients were recruited and 334 of them completed. Four clusters were identified; the oropharyngeal symptom cluster was the most severe and had the greatest interference with diet. Patients with pretreatment nutritional risk or malnutrition experienced more severe oropharyngeal symptom cluster. Conclusions Pretreatment nutritional risk or malnutrition could predict the oropharyngeal symptom cluster in patients with HNC undergoing radiotherapy.