In recent years, the application of polyvinyl chloride (PVC) material has significantly expanded within the realm of biomedical materials. However, the hydrophobicity of PVC has been found to cause many adverse reactions in patients within the biomedical field. It is imperative to urgently discover viable approaches for enhancing the hydrophilicity of PVC in order to ensure its safety in biomedical applications. In this study, the surface of PVC films was modified with a combination of hyperbranched polylysine (HBPL) and polydopamine (pDA) through either simultaneous deposition with polydopamine (PVC-pDA/HBPL) or successive deposition of pDA and HBPL (PVC-pDA-HBPL), aiming to investigate the influence of this modification method on surface hydrophilicity enhancement. The surface coatings were characterized using gravimetry, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, and water contact angle measurements. The results demonstrated that the incorporation of HBPL led to a significant enhancement in both the deposition amount and stability of pDA, particularly when the mass ratio of DA/HBPL was approximately 1:1. Simultaneously, the morphology of the films exhibited an increase in roughness, while surface hydrophilicity was significantly enhanced upon incorporating pDA and HBPL, and the water contact angle was decreased to 43.2°. Moreover, the detachment of PVC-pDA/HBPL and PVC-pDA-HBPL after exposure to 1.0 M NaOH solutions was considerably lower compared to that of PVC-pDA alone, indicating improved stability under strongly basic conditions. Notably, these enhancements were more pronounced for PVC-pDA/HBPL than for PVC-pDA-HBPL, indicating that HBPL may act as a cross-linker during pDA deposition primarily through intermolecular Schiff base reactions, hydrogen bonding, or Michael addition. This work represents a pioneering effort in integrating HBPL and dopamine for hydrophilic modification of PVC materials, thereby expanding the potential applications of PVC materials. Additionally, we provide novel insights into constructing a hydrophilic surface based on bionic principles and expanding the potential applications of HBPL and pDA.