Objective? To investigate the effect and safety of high-flow nasal cannula (HFNC) oxygen therapy for patients after extubation in lung transplantation. Methods? A retrospective study was conducted on 60 hospitalized patients with lung transplant during January 2017 to December 2017 in Wuxi People＇s Hospital. According to the different methods of respiratory support prescribed after extubation, the patients were divided into two groups: observation group (n=28, via HFNC) and control group (n=32, via nasal oxygen tube) . The two groups were compared in terms of the clinical indicators including their blood gas analysis(oxygenation index, lactic acid, partial pressure of carbon dioxide) , viscosity of sputum and comfort, etc. Results? Six hours after extubation and before transferring to other departments, the observation group＇s oxygenation index was(263.70±48.97)and(273.22±43.26)mmHg, which were statistically different from those of the control group with (217.83±77.30)and(229.08±68.64)mmHg respectively (P＜ 0.05). Before transferring to other departments, the partial pressure of carbon dioxide in the observation group was (37.04±8.56)mmHg, lower than the control group with (42.43±6.14)mmHg with a statistical difference (P＜0.05); the viscosity of sputum in the obseration group was lower than the control group with statistical difference (P＜0.05); the patients＇ comfort in the observation group achieved (7.72±1.06)points, higher than the control group＇s (4.39±0.82)points with statistical difference (P＜ 0.05). Conclusions? HFNC oxygen therapy for the patients after extubation in lung transplantation has good effects, is safe and reliable, and can be widely applied in clinical practice.