〔Abstract〕 Objective To study the effect of ultrasound-guided femoral nerve block (USFNB) combined with epidural analgesia (PCEA) on the level of inflammatory factors and the degree of pain in patients undergoing general anesthesia for lower limb orthopedic surgery. Methods 80 patients with lower extremity orthopaedic surgery under general anesthesia were selected from the First Affiliated Hospital of Xiamen University from June 2020 to June 2021, according to the random number table method, the patients were divided into control group and observation group, with 40 cases in each group. The control group was given PCEA, and the observation group was given USFNB combined with PCEA. The levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and the degree of pain were compared between the two groups of patients at different times after surgery. Results The levels of hs-CRP, TNF-α, and IL-6 in the two groups of patients decreased with time, and the levels of various inflammatory factors in the observation group at different times were significantly lower than those in the control group, and the differences were statistically significant (P < 0.05). The pain scores of the two groups decreased with time, and the pain scores of the observation group at different times were significantly lower than those of the control group, and the differences were statistically significant (P < 0.05). Conclusion USFNB combined with PCEA for patients undergoing general anesthesia for lower limb orthopedic surgery can significantly reduce the level of inflammatory factors in patients and significantly reduce their pain.