Abstract: Objective To evaluate the therapeutic effect of high flow nasal cannula(HFNC) in the treatment of diffuse lung disease patients with respiratory failure.Methods A total of 90 diffuse lung disease patients with respiratory failure who were admitted to Department of Respiration and Critical Care Medicine, the Affiliated Hospital of Xuzhou Medical University from January 2020 to December 2021 were enrolled. According to the corresponding modes of oxygen inhalation, they were divided into three groups(n=30): a HFNC group, a routine group and a noninvasive ventilation machine group. After oxygen inhalation, their cardiopulmonary functional indexes and overall indexes were analyzed and the curative effect of different oxygen inhalation methods on diffuse lung disease patients with respiratory failure were discussed.Results (1) Related indexes of cardiopulmonary function: After treatment for 15 days, all patients presented improvement in heart rate(HR), respiratory rate(RR) and mean arterial pressure(MAP), but the HFNC group showed remarkably improvement in the above indexes on post-treatment 7 and 15 days, compared the other two groups(P<0.05). After treatment for 15 days, the HFNC group showed significantly reduced sputum viscosity and removal times of oxygen therapy devices, compared with the other two groups(P<0.05). Furthermore, obvious improvement was seen as to pulmonary function, arterial blood gas analysis and oxygenation index(PaO₂/FiO₂) in the HFNC group and the non-invasive ventilation machine group, compared with the routine group(P < 0.05).(2) Overall indicators: The HFNC group had shorter length of hospitalization stay, better clinical effect and lower rate of 28-day intubation rate than the other two groups(P<0.05). During treatment, patients in the HFNC group and the routine group were more comfortable than the non-invasive ventilation machine group(P<0.05).Conclusions Application of HFNC in diffuse lung disease patients with respiratory failure has definite therapeutic effects. The patients show better recovery of cardiopulmonary function and shorter length of hospitalization stay, and are easier to get rid of the sputum, with more comfort during treatment process.