Disclosed is an anticoagulant polypeptide and applications thereof. The anticoagulant polypeptide comprises a polypeptide formed by an amino acid sequence as represented in Seq. ID No. 1; or comprises a derived polypeptide that selectively inhibits coagulation factor XIa and is formed by an amino acid sequence, as represented in Seq. ID No. 1, that has undergone one or multiple amino acid residue substitutions, deletions, or insertions. The anticoagulant polypeptide is a selective inhibitor for coagulation factor XIa, has anticoagulant activity and small side-effect, and can be used in preparing medicines for the prevention and treatment of thrombotic diseases.