Background: Tourniquet technique is often used in total knee arthroplasty (TKA), However, the effect on postoperative delirium (POD) in elderly patients with TKA procedure is still unknow.Methods: This prospective randomized controlled study assessed eligibility of 245 elderly patients, 197 patients met the inclusion criteria were randomly divided into tourniquet group (n=98) and non-tourniquet group (n=99). The primary outcome was the incidence of POD within 72 hours after surgery. The secondary outcome was the quality of rehabilitation, including inflammatory reaction, postoperative pain, hypoproteinemia and anemia.Results: Of 245 patients, 184 patients completed this clinical trial, 92 cases in each group. There were 14 patients (15.22%) with POD in tourniquet group and 5 patients (5.43%) in non-tourniquet group (95%CI 1.076 to 9.067, P=0.029). The changes of WBC, NEUT%, CRP, IL-6 and middle patellar circumference in tourniquet group were higher than those in non-tourniquet group (F=5.136, P=0.025 F=17.213, P<0.001 F=9.055, P=0.003 F=552.793, P<0.001 F=153.839, P<0.001). VAS at resting and activity in tourniquet group were higher than those in non-tourniquet group (F=170.102, P<0.001 F=75.391, P<0.001). There were 41 (44.57%) patients with hypoproteinemia in tourniquet group and 26 (28.26%) patients in non-tourniquet group (95%CI 1.106 to 3.765, P=0.022). Conclusion: The application of tourniquet technique in elderly patients with TKA procedure increased the incidence of POD, which may attribute to the increased inflammatory reaction, severe postoperative pain and hypoproteinemia caused by tourniquet technique. Trial registration: This prospective study (Ethics Committe and IRB number: 2019-338) was approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University ,Chongqing, China (Chairperson Prof Hao Jie) on 23 April 2021 and registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn, Chictr2100045711) before the enrolment process started on 28 April 2021, The study adhered to the CONSORT guidelines and written informed consent was obtained from all subjects participating in the trial.