Ｏｂｊｅｃｔｉｖｅ　To investigate the effect of ulinastatin combined with parecoxib on cognitive function in elderly patients undergoing combined thoracoscopic and laparoscopic esophagectomy. 　Methods　One hundred and sixty two cases of patients undergoing radical surgery for esophageal cancer were selected in our hospital. Patients were randomly divided into ulinastatin group(n=39), parecoxib group(n=41), combined group (n=42) and control group(n=40) by using random number tables method. Patients in the ulinastatin group were intravenously infused with 5 000 U/kg ulinastatin before skin incision, while in the parecoxib group were intravenous injected with 40 mg parecoxib, 10 min before induction of anesthesia. Patients in the combined group were intravenously infused with 5 000 U/kg ulinastatin before skin incision and intravenous injected with 40 mg parecoxib, 10 min before induction of anesthesia. Patients in the control group were given the same amount of normal saline according to the method of the combined group. The general conditions of patients in each group were recorded. Serum levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay(ELISA) at the time points of before operation(T0), operation completed (T1),postoperative 6 h (T2), postoperative 24 h (T3), postoperative 72 h (T4) respectively. The cognitive functions of patients in each group were evaluated by Mini-mental State Examination(MMSE) scale at the time points of T0, T3, T4 and postoperative 7 d(T5) respectively.　Results　Compared with the control group, the levels of MDA, IL-1β, IL-6 and TNF-α in the ulinastatin group at T1-T4, the parecoxib group and the combined group were decreased (P<0.05) while the levels of GSH-Px and SOD were increased (P<0.05). Compared with the ulinastatin group and the parecoxib group, at T1-T4, the levels of MDA, IL-1β, IL-6 and TNF-α in the combined group were decreased while the levels of GSH-Px and SOD were increased(P<0.05). Compared with the control group, at T3 and T4, the MMSE scores in the ulinastatin group, parecoxib group and the combined group were increased (P<0.05). Compared with the ulinastatin group and the parecoxib group, at T3 and T4, the MMSE scores in the combined group were increased (P<0.05). At T3, postoperative cognitive dysfunction incidence rates in the control group, ulinastatin group, parecoxib group and combined group were 35.0%, 23.1%, 24.4% and 14.3% respectively. All above parameters in the combined group was significantly lower than the control group (P<0.05).　Conclusions　Application of ulinastatin combined with parecoxib in elderly patients undergoing combined thoracoscopic and laparoscopic esophagectomy could effectively improve postoperative cognitive function. The mechanism might be related to reducing oxidative stress and inflammatory reaction.