Polyurethanes (PU) is widely applied in the blood-contact biomaterials. However, its biocompatibility still cannot meet the requirements for long-term service. In this work, a polydopamine (PDA) layer was first prepared on the PU surface, and then an anticoagulant polymer with an endothelial glycosaminoglycan-mimicking structure capable of catalyzing the release of nitric oxide (NO) gas molecules 6-arm-poly (ethy1ene glycol)-Heparin-Selenocystamine (PEG-Hep-SeCA) was grafted on the PDA-modified PU surface to construct a bioactive coating with the capacity to catalyze the release of NO from the endogenous donors. The findings indicated that the modified PU surfaces had excellent hydrophilicity, selective albumin adsorption as well as good blood compatibility and endothelial cell growth properties. The hemocompatibility and endothelial cell growth were further significantly improved in the case of catalytic NO generation. Therefore, the surface modification strategy of this study can significantly improve the biocompatibility of PU and thus lay the foundation for future clinical applications of medical polyurethane.