Soon after bone fracture, the initiation of the coagulation cascade results in the formation of a blood clot, which acts as a natural material to facilitate cell migration and osteogenic differentiation at the fracture site. The existence of hematoma is important in early stage of bone healing, but the persistence of hematoma is considered harmful for bone regeneration. Fibrinolysis is recently regarded as a period of critical transition in angiogenic-osteogenic coupling, it thereby is vital for the complete healing of the bone. Moreover, the enhanced fibrinolysis is proposed to boost bone regeneration through promoting the formation of blood vessels, and fibrinolysis system as well as the products of fibrinolysis also play crucial roles in the bone healing process. Therefore, the purpose of this review is to elucidate the fibrinolysis-derived effects on osteogenesis and summarize the potential approaches-improving bone healing by regulating fibrinolysis, with the purpose to further understand the integral roles of fibrinolysis in bone regeneration and to provide theoretical knowledge for potential fibrinolysis-related osteogenesis strategies.