Abstract: A nanobody or an antigen-binding fragment thereof against a specific region of a factor XII (FXII) is provided. The nanobody or the antigen-binding fragment thereof binds to FXII through a binding epitope for FXII to block the activation of FXII, and the binding epitope for FXII includes a conformational epitope. A neutralizing antibody for FXII screened by phage display is provided, and it has been found that the neutralizing antibody can treat thrombosis, myocardial ischemia-reperfusion injury (IRI), and vasculitis in mouse arterial thrombosis, rat extracorporeal membrane oxygenation (ECMO), mouse IRI, and vasculitis models.