To explore whether perioperative intravenous flurbiprofen axetil can reduce the incidence and intensity of chronic pain for breast cancer after surgical treatment.This randomized, double-blind, controlled trial enrolled 60 patients undergoing mastectomy and axillary lymph node dissection under general anesthesia. All patients accepted Hospital Anxiety and Depression Scale (HAD) tests the day before the surgery to evaluate depression and anxiety. The patients were randomly assigned to receive either 50 mg flurbiprofen axetil intravenously 15 minutes before the surgical incision and 6 hours later (group F) or intravenous 5 mL intralipid as a control (group C). All patients received patient-controlled intravenous analgesia (PCIA) with fentanyl postoperatively. Peripheral venous blood samples were drawn before the surgery, at 4 and 24 h after the surgery to detect the plasma level of PGE2 and tumor necrosis factor-α (TNF-α). Postoperative fentanyl consumption, Numerical Rating Scale (NRS) scores and adverse effects were recorded at 2, 6, 12, 24 and 48 h after the surgery. The duration and intensity of pain were followed up by telephone at the 2nd-12th month after the surgery.The incidence of pain at 2, 4, 6, and 12 months after the breast surgery was 33%, 20%, 15%, and 10%, respectively, and the average pain score was 0.77, 0.57, 0.28, and 0.18, respectively. Compared with group C, the scores of pain in group F were significantly lower at 2, 4, 6 and 12 months postoperatively (F=7.758, P=0.007). The incidence of pain in group F was significantly lower at 2, 4 and 6 months postoperatively (P0.05). Preoperatively and at 4 and 24 h after the surgery, there was no significant difference in the level of TNF-α between the two groups (F=0.530, P=0.470); but plasma concentration of PGE2 in group F was significantly lower than that in group C (F=5.646, P=0.021). No patients developed abnormal bleeding, peptic ulcer, impaired liver or renal function and respiratory depression.Perioperative intravenous infusion of 100 mg flurbiprofen axetil can decrease the intensity and incidence of chronic pain for breast cancer after surgical treatment.