Biofouling as a global problem has made detrimental impact on many fields, especially for marine industry. Polydimethylsiloxane-based coatings are environment-friendly and exhibiting good fouling release performance in the marine coating application. However, their intrinsic low surface energy and high hydrophobic character lead to poor fouling resistance property and weak adhesion to substrate. In this work, we firstly fabricate self-adhesive PDMS-based amphiphilic cross-linked coatings with good anti-biofouling performance via synthesizing dopamine methacrylamide which then copolymerized with mercaptopropyl methylsiloxane-dimethysiloxane, poly (ethylene glycol) diacrylate under UV photo-cross-linking. The coating exhibits devisable heterogeneous nanoscale mosaic chemical surfaces caused by micro phase segregation, effectively resistance to nonspecific protein adsorption and marine fouling organism (P. tricornutum) attachment which are mainly ascribed to the unique surface topography and chemical heterogeneity. Moreover, the resulting coatings exhibit significantly improved adhesion to substrates, due to complex interfacial catechol chemistry reaction. This simple design provides a novel methodology for preparing an efficient and eco-friendly anti-biofouling PDMS-based amphiphilic coating.