Polyurethane (PU) catheters are commonly used in clinical treatment. However, the hydrophobic nature of the PU catheter surface leads to adhesion or adsorption to platelets, proteins, bacteria, and other molecules when used in human treatment. To achieve a surface with strong hydrophilicity, high stability and excellent biocompatibility, it is necessary to functionalize the PU catheters. In this paper, a coating with antifouling function was constructed on the surface of PU catheters using plasma technology and an amide coupling reaction. A series of characterization methods, including X-ray photoelectron spectroscopy (XPS), water contact angles (WCA), and atomic force microscopy (AFM), were used to prove the successful modification of the polymer coatings. The coatings showed good stability under conditions such as PBS (pH 7.4, 720 h), 75% ethanol (6 h) and 1 wt% SDS (10 min). Additionally, the coatings exhibit excellent hemocompatibility and antibacterial properties. The PU/PEI/PCSB coating has the best anti-fouling performance among them, which means that using the PCSB copolymer has the potential to modify different clinical catheters into highly effective antifouling coatings.