A versatile hydrophilic and antifouling coating was designed and prepared based on catechol-modified four-arm polyethylene glycol. The dopamine (DA) molecules were grafted onto the end of the four-arm polyethylene glycol carboxyl (4A-PEG-COOH) through the amidation reaction, which was proven by 1H NMR and FTIR analysis, assisting the strong adhesion of PEG on the surface of various types of materials, including metallic, inorganic, and polymeric materials. The reduction of the water contact angle and the bacteria-repellent and protein-repellent effects indicated that the coating had good hydrophilicity and antifouling performance. Raman spectroscopy analysis demonstrated the affinity between the polymeric surface and water, which further confirmed the hydrophilicity of the coating. Finally, in vitro cytotoxicity assay demonstrated good biocompatibility of the coating layer.