Objective: To explore the associated risk factors of the acute mucosa reaction in patients with nasopharyngeal carcinoma after radiotherapy and chemotherapy and analyse the application efficacy of OREM self-protection theory for patients with nasopharyngeal carcinoma after radiation and chemotherapy therapy combined with acute mucosa reaction. Methods: Ninety-six cases nasopharyngeal carcinoma patients in our hospital from Jan. 2016 to Dec. 2019 were selected, all patients were treated with radiation and chemotherapy during the same period, they were divided into a combined group (n=81) and a non-combined group (n=15) according to combined with acute mucosa reaction or not after treatment. The general data of patients in 2 groups were for single factor analysis, and the risk factors of effecting the acute mucosa reaction of patients with nasopharyngeal carcinoma after radiation and chemotherapy therapy were explored by multivariable logistic regression analysis, the patients in combined group were treated with OREM self-protection theory, the self-protection concept, Visual Analog Scale (VAS) score and oral mucositis occurrence before and after intervention were compared. Results: There were 81 cases patients with acute mucosa reaction among the 96 cases patients with nasopharyngeal carcinoma after radiation and chemotherapy therapy, the incidence was 84.38%; the proportion of patients with a history of smoking and diabetes in combined group were higher than those in non-combined group; the hemoglobin (Hb) contents before radiation in in combined group was higher than that in non-combined group, and the white blood cell count was lower than that in non-combined group (P<0.05); multivariable logistic regression analysis showed that, had a history of smoking, diabetes, white blood cell count lower were the independent risk factors of combined with acute mucosa reaction of patients with nasopharyngeal carcinoma after radiation and chemotherapy therapy (OR=1.778, 4.457, 6.204; P<0.05); after OREM self-protection theory intervention, the self-protection concept score increased, VAS score decreased, and the proportion of patients with oral mucosa reaction with 0–II class increased compared with before intervention (P<0.01). Conclusion: With a history of smoking, diabetes, white blood cell count lower were the independent risk factors of combined with acute mucosa reaction of patients with nasopharyngeal carcinoma after radiation and chemotherapy therapy, the application of OREM self-protection theory intervention can enhance the self-protection concept, reduce oral pain, prevent and treat the oral mucosa reaction.