Abstract: Objective To explore the therapeutic effect of intramedullary nails combined with locking compression plate in patients with multi-segment tibial fractures, and to analyze correlation between transforming growth factor-β₁(TGF-β₁), fibroblast growth factor-2(FGF-2)and bone nonunion. Methods Eighty patients with multiple tibia fractures were randomly divided into observation group and control group, with 40 cases in each group. The control group was treated with locked compression plate, and the observation group was additionally combined with intramedullary nails. The efficacy changes and complications of the two groups were compared, and the impact of postoperative TGF-β₁ and FGF-2 levels on nonunion were analyzed. Results There were no significant differences in the operation time, intraoperative blood loss and hospital stay between the two groups(P>0.05). The fracture healing time in the observation group was shorter than that in the control group, and the difference was statistically significant(P<0.05). Before surgery, Ankle Joint Rating Scale(Kofoed)score showed no significant difference between the two groups(P>0.05), but was higher in the observation group than the control group after operation, the difference was statistically significant(P<0.05). There was no significant difference in the incidence of complications between the two groups(P>0.05). The levels of TGF-β₁ and FGF-2 in patients with nonunion were- lower intra-group than those without, and the difference was statistically significant(P<0.05). There were no significant between-group differences in the levels of TGF-β₁ and FGF-2 in patients with nonunion and without(P>0.05). Conclusion The use of intramedullary nails combined with locking compression plate in the treatment of multiple tibial fractures can shorten healing time of the fracture, reduce the incidence of complications, and promote the recovery of ankle function. The levels of TGF-β₁ and FGF-2 can effectively determine whether the patient has bone nonunion or not, which is of great significance for the early formulation of treatment measures.