Objective To investigate the prevention and treatment effect of low-temperature oxygen atomization inhalation (LTOAI) in patients with nasopharyngeal carcinoma with radiation-induced oral mucositis (RIOM). Methods A total of 101 patients with nasopharyngeal carcinoma who received radiotherapy were randomly divided into an intervention group (n=47) and a control group (n=54). During radiotherapy, the two group received inhalation therapy with a mixture of saline and 150 μg granulocyte colony stimulating factor (G-CSF).The control group was subjected to room temperature ultrasonic atomization inhalation (RTUAI), while the intervention group to LTOAI. Results There were significant differences in the severity of RIOM, the duration of RIOM, the time to RIOM onset, and saliva flow rate (SFR) between the 2 groups, with all outcomes favoring the intervention group (all P＜0.05). However, there was no significant difference in the incidence rate of RIOM and oral pH value when the radiation dose reached 33 Gy, between the two groups (P＞0.05 for both). Conclusion LTOAI can mitigate RIOM in nasopharyngeal carcinoma patients receiving radiation therapy, delay the onset and shorten the duration of RIOM. Meanwhile, LTOAI plays some role in protecting the saliva glands and maintaining the internal environment of the oral cavity.