Objective To investigate the clinical efficacy of preemptive analgesia with parecoxib sodium in the treatment of postoperative analgesia of knee osteoarthritis with artificial knee joint replacement and the levels of IL-6, IL-10 and TNF-α in serum.Methods Totally 100 patients with knee osteoarthritis from January 2017 to September 2019 were collected. All patients underwent artificial knee arthroplasty. The patients were randomly divided into experimental group and control group, 50 cases in each group. The control group did not undergo any preemptive analgesia. The experimental group received intravenous injection of parecoxib sodium 40 mg before anesthesia. Both groups received intravenous sufentanil for controlled analgesia. Pain scores were performed using VAS and MMSE for cognitive function scoring in 1 h before surgery, 6 h after surgery, 12 h after surgery, 24 h after surgery, and 48 h after surgery. The expression levels of IL-6, IL-10 and TNF-α in serum were determined by ELISA.Results VAS scores of patients in the two groups gradually decreased with the extension of time, and the scores in the experimental group were lower than those in the control group at the 6 h, 12 h, 24 h, and 48 h after surgery, with statistically significant differences (P < 0.05). The HSS knee score gradually increased with the extension of time, and the scores of the experimental group were lower than those of the control group at 12 h, 24 h and 48 h after surgery, with statistically significant differences (P < 0.05). The levels of IL-6 and TNF-α were increased in both groups after surgery, but were lower in the experimental group at the 6 h, 12 h, 24 h, and 48h after surgery, with statistically significant differences (P < 0.05). After the operation, IL-10 concentration in both groups was decreased, and it was higher in the experimental group at the 6 h, 12 h, 24 h, and 48 h after the operation, with statistically significant difference (P < 0.05). In the early postoperative period, cognitive function scores of both groups decreased, but those of the experimental group were higher at 6 h, 12 h, 24 h and 48 h after surgery. In addition, the total adverse reaction rate of 6.0% in the experimental group was lower than 16.0% in the control group.Conclusion Preemptive analgesia with parecoxib is effective in the treatment of postoperative analgesia of knee osteoarthritis with artificial knee joint replacement, and significantly reduces the level of postoperative inflammatory factors, increases the level of anti-inflammatory factors, protects patients' cognitive function effectively, and reduces the inflammatory response and adverse reactions.