Sepsis is a clinical syndrome which results from severe infection and systemic inflammatory response. Deregulated interplay between inflammation and coagulation plays a pivotal role in the pathogenesis of sepsis. Thrombomodulin is an endogenous anticoagulant protein that possesses both anti-inflammatory and anticoagulant properties in directly and indirectly ways, which provides a new choice for the treatment of sepsis. The structure, function and application of thrombomodulin in the treatment of sepsis are introduced in this paper.