Objective To explore the effect of heated humidified high-flow oxygen therapy with the combination use of MR850 humidifier with Venturi mask in patients after esophageal cancer surgery. Method Totally, 135 patients who underwent esophageal cancer surgery were randomly divided into 2 groups .The control group (n=67) received conventional oxygen therapy, while the intervention group (n=68) received heated humidified high-flow oxygen therapy. The comfort levels, vital signs, sputum viscosity, expectoration effect between the two groups were compared. Results The total comfort scores for oxygen therapy, the oxygen saturation level (PaO2 ) on the 3rd postoperative day in the intervention group were significantly higher than those in the control group; the sputum viscosity of the intervention group was thinner and the expectoration effect was better in the intervention group than the controls (P<0.01 for all). Conclusion Heated humidified high-flow oxygen therapy with the combination use of MR850 humidifier with Venturi mask can improve comfort level of oxygen therapy among patients after esophageal cancer surgery, and promote sputum discharge.