Objective To compare the clinical effects of high-flow Nasal Cannula oxygen therapy and low-frequency continuous positive airway pressure ventilation in patients at high risk of weaning and to avoid or shorten the supporting time of in effective oxygen therapy. Methods Patients who met routine weaning procedures and had at least one high risk factor for weaning were randomly assigned to CPAP group (n=69) or HFNC group (n=71), CPAP group received CPAP therapy, HFNC group received HFNC therapy, observed for 48 h under the same medical and nursing conditions. Results The respiratory frequency and pain scores of patients in HFNC group were lower than those in CPAP group at 24 h and 48 h (P<0.05). Conclusion HFNC can improve breathing and reduce pain in patients at high risk of weaning.