Stereotactic radiotherapy (SBRT) is widely used in the treatment of thoracic cancer.To evaluate the efficacy of a non-rebreather mask (NRBM) and high-flow nasal cannula (HFNC) in patients with radiation pneumonia complicated with respiratory failure.This was a single-center randomized controlled study. Patients admitted to the EICU of the Fourth Hospital of Hebei Medical University were selected and divided into NRBM and HFNC group. Arterial blood gas analysis, tidal volume, respiratory rates and the cases of patients receiving invasive assisted ventilation were collected at 0, 4, 8, 12, 24, 48, and 72 h after admission.(1) The PaO2/FiO2, respiratory rates, and tidal volume between the two groups at 0, 4, 8, 12, 24, 48, and 72 h were different, with F values of 258.177, 294.121, and 134.372, all P< 0.01. These indicators were different under two modes of oxygenation, with F values of 40.671, 168.742, and 55.353, all P< 0.01, also varied with time, with an F value of 7.480, 9.115, and 12.165, all P< 0.01. (2) The incidence of trachea intubation within 72 h between HFNC and NRBM groups (23 [37.1%] vs. 34 [54.0%], P< 0.05). The transition time to mechanical ventilation in the HFNC and NRBM groups (55.3 ± 3.2 h vs. 45.9 ± 3.6 h, P< 0.05). (3) The risk of intubation in patients with an APACHE-II score > 23 was 2.557 times than score ⩽ 23, and the risk of intubation in the NRBM group was 1.948 times more than the HFNC group (P< 0.05).Compared with the NRBM, HFNC can improve the oxygenation state of patients with radiation pneumonia complicated with respiratory failure in a short time, and reduce the incidence of trachea intubation within 72 h.