The prognosis of Achilles tendon rupture is often unsatisfactory. Proliferative fibrous tissues and disordered collagen bundles make it difficult to guarantee normal biomechanical properties. The present study aimed to investigate the role of fibroblast growth factor-2 (FGF-2) in promoting the ability of human tendon-derived stem cells (hTDSCs) to treat Achilles tendon injury. hTDSCs were isolated from fetal Achilles tendon tissue and verified using fluorescence activated cell sorting analysis and multidirectional differentiation. The cells were then transfected with a lentivirus carrying the FGF2 gene. In vitro, FGF2 overexpression increased the expression of Collagen Type III Alpha 1 Chain (collagen-III) and scleraxis BHLH transcription factor (SCXA) significantly. Additionally, FGF-2-hTDSCs were transplanted into a rat Achilles tendon defect model. The in vivo results showed that the Achilles tendon tissue in the FGF-2 group secreted more extracellular matrix and produced collagen fibers that showed a more orderly arrangement. The expression of collagen-I and III in the FGF-2 group was significantly increased at 4 weeks postoperatively compared with the control group. Moreover, biomechanical tests showed that the failure load of FGF-2 group was higher at 4 and 8 weeks postoperatively than that of the controls. FGF-2 group had the highest stiffness in the early postoperative period, but showed no significant difference in the middle and late postoperative periods compared with that of the controls. In conclusion, FGF2 gene-modified hTDSCs promoted healing of Achilles tendon injury more effectively than hTDSCs alone. (C) 2019 Elsevier Inc. All rights reserved.