Abstract: Thrombosis has serious impact on people's quality of life, and its morbidity has an increasing tendency year by year. Currently available treatments are mainly anticoagulants. Although these anticoagulants have better antithrombotic effects, they are often associated with bleeding risk. Recent study revealed that coagulation factor Ⅺa (FⅪa) inhibitors can reduce the incidence of venous thrombosis without any effect on bleeding, which was of great importance in the treatment of thrombotic diseases. Therefore, FⅪa inhibitors have the potential to be developed into a new type of antithrombotic drugs. Recent advances in the research of small molecular FⅪa inhibitors derived from natural products and produced by chemical syntheses are reviewed, so as to provide reference for new drug design and discovery of FⅪa inhibitors.