Surface modification is widely employed to enhance the interfacial performance of blood-contacting medical devices. Among various strategies, polymer brushes through the “grafting-from” method have proven effective for constructing polymeric surfaces with defined functionalities. This approach relies on anchoring polymerization initiators onto a substrate to enable surface-initiated polymer growth; however, it often involves complex processing steps. As an alternative, surface segregation offers a route that enriches the surface with selected molecules during fabrication, allowing modification without additional treatments. In this work, we designed and synthesized a cyclic oligomeric initiator (Cy-I) that promotes surface segregation and conveys initiating groups on TPU substrates. Polymer brushes generated using Cy-I exhibit higher grafting density, enhanced stability, and superior antifouling performance compared with those from linear or low-molecular-weight initiators.