Objective：To investigate the application value of high-flow nasal cannula （HFNC）in high-risk patients with extubation failure based on the ultrasound-measured diaphragmatic-rapid shallow breathing index （D-RSBI）. Methods：Patients with mechanical ventilation for more than 48 hours in ICU from September 2017 to November 2019 were selected. Based on the extubation procedure after the SBT，their D-RSBI was measured using ultrasound and those whose D-RSBI ≥ 1.3 times/（min·mm） were evaluated as high-risk patients with extubation failure，who were randomized into two groups：HFNC group and conventional oxygen therapy group （COT group）；The re-intubation rate at 48 h after extubation and，respiratory rate （RR），heart rate （HR），arterial oxygen saturation （SaO2），arterial carbon dioxide partial pressure （PaCO2），oxygenation index （PaO2/FiO2）after extubation at 6 h，24 h，48 h were compared between the two groups. Results：A total of 41 patients who met the inclusion criteria were finally included in this study，of which 21 were in the HFNC group and 20 were in the COT group；RR，HR，SaO2，PaO2/FiO2 in the HFNC group were superior to the COT group at 6，24 h after extubation，the difference was statistically significant （P < 0.05）；and there was no significant difference between the two groups of PaCO2（P > 0.05）；SaO2，PaO2/FiO2 in the HFNC group was significantly higher than that in the COT group 48 h after extubation，and the difference was statistically significant （P < 0.05）；and there was no significant difference between the two groups of RR，HR，and PaCO2 （P > 0.05）. The re-intubation rate at 48 h after extubation in the HNFC group was 4.76%，the re-intubation rate in the COT group was 30.00%，and the difference was statistically significant （P < 0.01）. Conclusion：For patients with high-risk of extubation failure based on D-RSBI assessment，the use of HFNC after extubation can significantly improve the patient’s respiratory function and oxygenation，and significantly reduce the re-intubation rate，which is an ideal sequential treatment strategy.