Hemolysis of red blood cells (RBCs) caused by implant devices in vivo and nonpolyvinyl chloride containers for RBC preservation in vitro has recently gained much attention. To develop blood-contacting biomaterials with long-term antihemolysis capability, we present a facile method to construct a hydrophilic, 3D hierarchical architecture on the surface of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS) with poly(ethylene oxide) (PEO)/lecithin nano/microfibers. The strategy is based on electrospinning of PEO/lecithin fibers onto the surface of poly [poly(ethylene glycol) methyl ether methacrylate] [P(PEGMEMA)]-modified SEBS, which renders SEBS suitable for RBC storage in vitro. We demonstrate that the constructed 3D architecture is composed of hydrophilic micro- and nanofibers, which transforms to hydrogel networks immediately in blood; the controlled release of lecithin is achieved by gradual dissolution of PEO/lecithin hydrogels, and the interaction of lecithin with RBCs maintains the membrane flexibility and normal RBC shape. Thus, the blood-contacting surface reduces both mechanical and oxidative damage to RBC membranes, resulting in low hemolysis of preserved RBCs. This work not only paves new way to fabricate high hemocompatible biomaterials for RBC storage in vitro, but provides basic principles to design and develop antihemolysis biomaterials for implantation in vivo.