Salivary proteins of ticks can inhibit host hemostatic and inflammatory responses during the blood-sucking process of the parasites. A cDNA sequence, Hq021, was identified from a cDNA library of Haemaphysalis qinghaiensis. Hq021 encodes a mature protein containing 182 amino acids with a molecular mass of 20.5 kDa. The protein is rich in basic amino acids (lysine and arginine) at its C-terminus. Identification of no homologous proteins in databases suggested its novelty. A recombinant protein expressed with the cDNA in Escherichia coli could prolong the activated partial thromboplastin time (aPTT) of human plasma. We designated this basic tail-protein as Qinghaienin. Although Qinghaienin did not inhibit the amidolytic activities of some coagulation factors, it dose-dependently inhibited the generation of FXIIa, FXIa and kallikrein in plasma in the presence of silica-based aPTT reagent. By competing with FXII for the negatively-charged binding sites, Qinghaienin inhibited the activation of the zymogen and the coagulation processes. These findings suggest that Qinghaienin plays a critical role in both anticoagulation and anti-inflammatory processes during tick feeding and could serve as a potential candidate for the developing tick-derived anticoagulants.