Abstract: Objective To evaluate the clinical effects of transnasal high flow oxygen therapy (HFNC) in neonates with severe pneumonia and respiratory failure. Methods 54 neonates with severe pneumonia and respiratory failure in our hospital from Mar 1, 2017 to Feb 28, 2018 were randomly divided into observation group（27 cases） and control group（27 cases） with digital table method. The observation group were received with HFNC, and the control group with oxygen humidification device with ordinary Bubble Type for double nasal congestion 0.5-2 L/min. The heart rate, respiratory rate, PaO2, PaCO2 and SpO2 changes were evaluated before treatment, treatment for 1 h, 12 h and 24 h in both groups, at the same time, sputum viscosity, tracheal intubation mechanical ventilation rate, continuous positive airway pressure (CPAP), NICU stay time were compared in the course of treatment of difference. Results Through two different methods of treatment, the heart rate, respiratory rate, PaO2, PaCO2, SpO2were（138.75±5.18） times/ min,（44.46±3.06） times/ min,（95..67±8.61） mmHg,（45.33±4.61） mmHg,（93.08±3.96） ％ in the observation group, respectively, compared with （148.04±7.62） times/ min,（52.44±5.76） times/ min,（80.48±13.70） mmHg,（50.13±3.92） mmHg and（91.13±8.01） ％ in the control group, which had significant differences( t= 3.197, 5.510, -2.314, 3.406, -2.005, P < 0.05); The NICU stay time in observation group was( 175.2±46.15) h, respectively, which was much shorter than that in the contorl group(261.61±69.28) h, the difference was statistically significant (t=4.406,P＜0.05); Comparison of sputum viscosity between observation group and control group, which had significant differences( Z=3.25, P＜0.05). Conclusions HFNC is a new and effective way of oxygen therapy that can effectively treat neonates with severe pneumonia and respiratory failure, which can effectively relieve symptoms, improve lung oxygenation, reduce complications and improve prognosis.