[Objective] To explore the effect of Esketamine on tourniquet injury in patients with knee arthroplasty. [Methods] From January 2021 to January 2023, 106 patients with knee arthroplasty were divided into two groups: 53 cases were treated with Esketamine (medication group), and 53 cases were treated with conventional general anesthesia (non medication group). Compare two groups of clinical and laboratory data. [Results] Both groups of patients successfully completed the operation. MAP and HR increased significantly in the non medication group at 60min after applying tourniquet (P＜0.05), which decreased significantly in the non medication group at 10min removing tourniquet (P＜0.05). The NRS scores of the non medication group increased at 12 hours, 48 hours, and 7 days after surgery compared to the medication group (P＜0.05). The femoral circumference of the non medication group decreased 7 days after surgery compared to 12 hours after surgery (P＜0.05), the femoral circumference of the non medication group was lower than that of the medication group 7 days after surgery (P＜0.05), and the incidence of postoperative delirium in the medication group was lower than that in the non medication group (P＜0.05). The level of IL-6, LA and MDA in the non medication group increased significantly when the tourniquet removed for 10 minutes (P＜0.05). [Conclusion] Esketamine can inhibit tourniquet hypertension, relieve tourniquet pain and prevent quadriceps femoris muscle atrophy during knee arthroplasty.