In clinical extracorporeal membrane oxygenation (ECMO), prolonged blood residence time in oxygenators can lead to thrombus formation and complications. Heparin-based bioactive coatings are commonly used for anticoagulation, but prolonged shear stress during blood flow can cause heparin desorption, degradation, and inactivation, reducing durability and antithrombotic efficacy. In this study, we developed a silk fibroin (SF)-based multilayer coating to enhance both mechanical stability and anticoagulant performance. A SF foundation layer was first fabricated on hollow-fiber membranes using layer-by-layer (LbL) self-assembly. Then SF acted as a bridge to assemble heparin and albumin through electrostatic interactions, followed by crosslinking to stabilize the structure, resulting in a uniform SF-heparin-albumin composite coating with controllable thickness. 10-day shear oscillation and nanoscratch tests showed that the SF bridging layer significantly improved mechanical robustness and interfacial adhesion. In vitro and in vivo blood circulation assays demonstrated hemocompatibility, with reduced platelet adhesion, prolonged coagulation time, and enhanced antithrombotic performance. Blood-gas exchange tests using a miniaturized oxygenator confirmed that the coating did not impair gas transfer efficiency. In summary, the SF bridging layer effectively links the substrate to bioactive components, improving long-term mechanical integrity and anticoagulant properties without compromising oxygenator function.