Purpose: Postoperative cognitive dysfunction (POCD) characterized as the decline of memory and executive function after major surgery is not well illustrated. The aim of this study is to discover whether inflammatory cytokines and urinary trypsin inhibitor (uTi) contribute to the development of POCD. Method: Sixty-three patients undergoing lumber discectomy and 47 age-matched control volunteers were involved in this study. The level of C-reaction protein (CRP) and uTi/urine creatinine (Ucr) was measured by immunoturbidimetry and enzyme-inhibition assay, respectively. Meanwhile, ELISA was involved to detect the level of IL-6, IL-10, MMP-9 in serum. Montreal Cognitive Assessment (MoCA) test was used to determine the cognitive decline of the patients and age-matched controls. Result: In POCD group, the level of IL-6, IL-10, CRP, MMP-9 in serum and uTi /Ucr in urine was significantly higher than that in the group without POCD. The POCD was more frequently observed in elderly group than in the middle-aged group (43.75% versus 19.35%, p = 0.038). After logistic regression analysis adjusted by the age, only serum CRP at 72 h postoperation and urinary uTi /Ucr at 24 h postoperation were the independent risk factors of POCD. Conclusion: Age-related increasing proinflammatory postoperation may result in higher occurrence of POCD in the elderly. Additionally, patients with extremely high concentrations of CRP in serum at 72 h postoperation and uTi /Ucr in urine at 24 h postoperation are more likely to experience POCD, especially in the elderly.