To observe the effect of early nutritional intervention on radiation-induced oral mucositis and nutritional status in patients with head and neck cancer (HNC). A total of 54 HNC patients were divided into early (28 cases) and late (26 cases) nutritional intervention groups. The early group received enteral nutrition at the beginning of radiotherapy (RT), while the late group received enteral nutrition after restricted feeding. Operators reported and assessed the timing and extent of oral mucositis and nutritional status during treatment. The nutritional status assessment indicators included body weight; body mass index (BMI); Patient-Generated-Subjective Global Assessment (PG-SGA) score; levels of albumin, hemoglobin and pre-albumin and total lymphocyte count. The incidence of high-grade oral mucositis was significantly lower in the early group than that in the late group (P < 0.05). Nutritional status assessments showed more significant weight and BMI losses in the late group than in the early group at weeks 4 and 7 after RT (P < 0.01). The albumin decreased in the late group at week 7 after RT was more significant than that in the early group (P < 0.05). Albumin, hemoglobin and pre-albumin levels and total lymphocyte count decreased significantly in both groups (P > 0.05). During therapy, more patients in the early group were well-nourished and fewer were malnourished according to PG-SGA scores (P < 0.05). Early nutritional intervention can reduce the incidence of high-grade oral mucositis during RT in patients with HNC and improve the nutritional status during treatment, which has important clinical significance.