Abstract: Factor Xa is a trypsin-like serine protease playing a pivotal role in the blood coagulation cascade.Factor Xa and its inhibitors are of great importance in the development of orally active antithrombotic agents and have aroused considerable attention from the pharmaceutical industry sector over the years.In this review，the structural characteristics of the factor Xa binding site are discussed and the X-ray information available together with the published structure-activity relationship data is used to identify the molecular interactions that are most important for tight enzymeinhibitor binding，which would be useful in the structurebased drug design of novel factor Xa inhibitors.