Objective To investigate the efficacy of preoperative lower extremity nerve block on postoperative cognition in elderly patients undergoing total knee artbroplasty under general anesthesia. Methods In this study 117 cases of elderly patients undergoing total knee artbroplasty were divided into general anesthesia control group(n = 38), preoperative block group (n = 39) and postoperative block group (n = 40). The patients in the preoperativeblock group were injected with 20 ml of 0.375% Ropivacaine around the femoral nerve under ultrasound guidance immediately before induction of anesthesia, while the patients in the postoperative block group had the same femoral nerve block immediately after surgery. The serum level of S100β protein was detected before surgery (T0), 6 h (T1), 12 h (T2), 1 d (T3), 3 d (T4) and 7 d (T5) after surgery. At T0, T1, T3, T4 and T5, the MMSE scores were evaluated respectively. Results The serum levels of S100β protein at T1-T5 in the preoperative block group and the postoperative block group were lower than those in the general anesthesia control group, and the serum levels of S100β protein at T1-T5 in the preoperative block group were lower than the postoperative block group (P < 0.05).The MMSE scores at T1-T5 in the preoperative block group and the postoperative block group were higher than those in the general anesthesia control group, and the MMSE scores at T1-T4 in the preoperative block group were higher than those in the postoperative block group (P < 0.05). The dosages of Remifentanil and Propofol in the preoperative block group were lower than those in the postoperative block group and the general anesthesia control group, the analgesic remedy rate was lower than that in the postoperative block group and the general anesthesia control group (P < 0.05). The postoperative incidences of nausea and vomiting in the preoperative block group were significantly lower than those in the general anesthesia control group (P < 0.05). Conclusions Preoperative lower extremity nerve block could improve the postoperative cognitive function of elderly patients undergoing total knee artbroplasty under general anesthesia.