Objective：To investigate the combined physiologic effects of different positive end-expiratory pressure（PEEP）and decreased inspired oxygen fraction（FiO2）during one lung ventilation（OLV）. Methods：This study is a prospective，single-blind，randomized controlled study. One-hundred and twenty patients were equally randomized into four groups of A（OLV with 0 cmH2O），B（OLV with 5 cmH2O），C（OLV with 8 cmH2O），and D（OLV with 10 cmH2O）. All patients breathed an inspiratory oxygen fraction of 0.6. Arterial blood and venous blood were taken for gas analysism，and intrapulmonary shunt rate（Qs/Qt）were calculated before OLV（T1），OLV 10 min（T2），OLV 15 min（T3），OLV 30 min（T4），OLV 60 min（T5），and OLV 120 min（T6）. Haemodynamics and respiratory mechanics parameters were monitored continuously. The clinical pulmonary infection score（CPIS）was recorded on the second day after the surgery and the incidence of postoperative pulmonary complication was recorded. Results：Among the 120 patients assessed for eligibility，118 completed the study. At T2~T6，PaO2 in group D was significantly higher than that in group A，Qs/Qt in group D was significantly lower than that in group A（P < 0.05）. At T3~T4，PaO2 in group C was significantly higher than that in group A，Qs/Qt in group C was significantly lower than that in group A（P < 0.05）. At T4，PaO2 in group B were significantly higher than that in group A，Qs/Qt in group B were significantly lower than that in group A（P < 0.05）. At T2~T5，PaO2 in group D were significantly higher than that in group B，At T2 ~ T4，Qs/Qt in group D were significantly lower than that in group B（P < 0.05）. At T5，PaO2 in group D were significantly higher than that in group C（P < 0.05）. At T2~T6，driving pressure（DP）in group B，C，and D were significantly lower than that in group A（P < 0.05）. At T2~T5，DP in group C and D were significantly lower than that in group B（P < 0.05）. At T4~T6，dynamic compliances in group C and D were significantly higher than those in group A and B（P < 0.05）. The CPIS score was significantly lower in group B，C and D than that in group A on the second day after the surgery（P < 0.05）. Conclusion：During one lung ventilation with 0.6 FiO2，10 cmH2O PEEP improves pulmonary function without changing the hemodynamic parameters and reduces driving pressure，and plays an important role in lung protection.