Ｏｂｊｅｃｔｉｖｅ　To observe the effects of ulinastatin conbined with dexmedetomidine(Dex) on early postoperative cognitive function in elderly patients undergoing esophageal cancer operations.　Methods　Sixty patients (ASA Ⅰ-Ⅲ, aged 65-84 y) scheduled for surgeries for esophageal cancer were randomized into intervention group (group Ⅰ, n=30) and control group (group Ⅱ, n=30). After intravenous induction and tracheal intubation, the patients in the intervention group Ⅰ were infused intravenously 2×105 U ulinastatin in 100 ml normal saline in 30 min and Dex 0.5 μg·kg-1·h-1 to 30 min before end of the operation, the patients in group Ⅱ received the same volume of saline infusion only. Comprehensive neuro-psychological tests were performed at day 1 before and day 1, 3 after operation to assess preopereative cognitive function of patients. Peripheral artery blood was extracted to determine levels of serum S-100β protein, neuron-specific enolase(NSE) and IL-6 with ELISA before anesthesia induction(T0), at the end of the surgery(T1), and at day 1(T2) and day 3(T3) after operation.　Results　The difference between the test scores before and after the operation (X values) was significantly smaller in the group Ⅰ than in the group Ⅱ(P<0.05). The group Ⅰ showed a significantly lower incidence rate of postoperative cognitive dysfunction (POCD) than the group Ⅱ(6.7% vs 30.0%, P<0.05). Compared with the group Ⅱ, the group Ⅰ exhibited significantly lower serum levels of S-100β protein, NSE and IL-6 at T1(P<0.05), significantly lower NSE and IL-6 levels at T2(P<0.05) time point, and significantly lower IL-6 level at T3(P<0.05).　Conclusions　Intravenous injection of ulinastatin and Dex during the operation can reduce the incidence of POCD in elderly patients undergoing surgeries for esophageal tumors possibly in relation to decreased serum S-100β, NSE and IL-6 levels.