To investigate quality of life and influencing factors in patients with nasopharyngeal carcinoma during tomotherapy. Methods The nasopharyngeal carcinoma patients who received tomotherapy from November 2017 to May 2019 were enrolled for the study in the Chinese PLA General Hospital. EORTC QLQ⁃C30 questionnaires were used to evaluate the quality of life, the factors affecting the quality of life of the nasopharyngeal carcinoma patients were screened by multivariate analysis. Results There were 91 patients who completed questionnaires and submitted successfully. Physical function, cognitive function, loss of appetite, nausea and vomiting, fatigue were correlated with the risk of malnutrition (P<0.05), pain and tumor staging was correlated (P<0.05). The correlation between global quality of life and concomitant diseases was statistically significant (P<0.05). After tomotherapy, the scores of global quality of life and functional areas of patients were lower than those before tomotherapy (P<0.05), and the scores of symptom areas were higher than those before radiotherapy (P<0.05). The degree of pain after tomotherapy was significantly correlated with oral mucositis (P<0.05). Loss of appetite, nausea and vomiting, insomnia, fatigue and constipation were correlated with acute pharyngoesophagitis (P<0.05). There was a significant correlation between the changes of total health level, physical function and nutritional status during radiotherapy (P<0.05). Conclusion The quality of life of the nasopharyngeal carcinoma patients decreased after tomotherapy. Quality of life and treatment compliance of the patients can be improved by reducing adverse radiation reactions, improving the nutritional status and controlling concomitant disease symptoms.