Abstract: OBJECTIVE To explore the expressions of microRNA-223 (miR-223) and consanguinity signal protein of drosophila melanogaster (Smad) in peripheral blood of open lower limb fracture patients with postoperative infection and analyze the diagnostic values. METHODS A total of 350 patients who underwent internal fixation in orthopedics department of Jiande First People's Hospital due to open lower limb fracture from Dec 2018 to Dec 2021 were recruited as the research subjects and were divided into the infection group with 32 cases and the no infection group with 318 cases according to the status of postoperative infection.The wound secretions specimens were collected by aseptic means, pathogens were isolated and identified.The fasting venous blood specimens were collected after the surgery for 2 days, the levels of inflammatory factors C-reactive protein, tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), procalcitonin (PCT) and the expression levels of miR-223, Smad pathway proteins as well as upstream and downstream factors transforming growth factor-β(TGF-β), vascular endothelial growth factor (VEGF) were detected. RESULTS The incidence rate of postoperative infection was 9.14% among the patients with open lower limb fracture patients.Gram-positive bacteria were dominant among the isolated pathogens, accounting for 63.16%.There were significant differences in age, complication with diabetes mellitus, intraoperative blood loss volume, postoperative drainage volume and bedridden time between the two groups(P＜0.05).The levels of postoperative IL-6, TNF-α, CRP and PCT of the infection group were higher than those of the no infection group(P＜0.05); the levels of miR-223, Smad1, Smad2, Smad3, TGF-β and VEGF of the infection group were higher than those of the no infection group (P＜0.05).The areas under curves (AUCs) were more than 0.7 in prediction of postoperative infection in the patients with open lower limb fracture patients, and the predictive efficiencies were high. CONCLUSION The postoperative infection may lead to the abnormal expressions of miR-223 and Smad pathway proteins in peripheral blood of the patients with open lower limb fracture, and the indexes have high values in prediction of postoperative infection.