〔Abstract〕 Objective To investigate the effects of protective ventilation on the production of interleukin(IL)-1β,IL-18 and endogenous melatonin and prognosis of patients with esophageal cancer. Methods Ninety esophageal cancer patients were randomized to receive “conventional”ventilation( Vt = 10 ml/kg) or lung protective ventilation [Vt = 5 ml/kg along with 5 cm H2O positive end-expiratory pressure( PEEP) ]. IL-1β,IL-18 and melatonin in bronchoalveolar lavage fluid( BALF) and serum were measured before and at the end of the operation. Respiratory variables during two-lung ventilation,one-lung ventilation for 30 min and at the end of the operation were recorded. Results of blood gas analysis on the first day after surgery and outcomes were evaluated. Results Compared with “conventional”ventilation group,lung protective ventilation decreased peak airway pressure( Ppeak),plateau airway pressure( Pplat) and driving pressure( ΔP). Lung protective ventilation increased the partial pressure of oxygen on the first day after surgery and lowered the blood lactic acid values( P<0. 001). In addition,lung protective ventilation reduced the incidence of postoperative pulmonary complications( P = 0. 045) and the rate of major postoperative complications( P = 0. 028). Moreover,lung protective ventilation not only suppressed alveolar and serum IL-1β and IL-18 secretion,but also restored the level of endogenous melatonin( P<0. 001).Conclusion Lung protective ventilation suppresses IL-1β and IL-18 secretion,restores the level of endogenous melatonin and reduces the incidence of postoperative lung and total complications.