Antifouling coatings are crucial to protect marine facilities and aquacultures from the damage of microorganisms for long-term serves. However, it is still a challenge to fabricate coating with excellent antifouling performance and superior mechanical stability. Here, we report a bio-based amphiphilic hydrogel coating with excellent antifouling and mechanical properties. The coating was achieved by the in-situ formation of hydrophobic and hydrophilic interpenetrating polymer network (IPN). The hydrophobic part from a synthesized silicon-containing epoxy resin contributes to superior mechanical properties including high tensile strength and excellent adhesion of 5B. While the hydrophilic hydrogel part from the cross-linking of a hydrophilic polymer with AgNPs gives excellent antifouling properties, resist to proteins, bacteria, algae, and other marine organisms. The antifouling performance of the coating was evaluated by the attachment of proteins (BSA-FITC), bacteria (Escherichia coli and Bacillus subtilis), and Algae (Navicula torguatum and Phaeodactylum tricornutum). The results show that the bio-based amphiphilic hydrogel coating (e.g. SA-1-5) endows surface with excellent resistance to the fouling of proteins, bacteria and microorganisms. The overall antifouling and mechanical properties of the amphiphilic coating was also evaluated by field test in East China Sea from June 3rd 2020 to July 17th 2020 that the bio-based amphiphilic hydrogel coating was intact and almost no marine organisms attached. This work provides a new strategy for the fabrication of bio-based and high-performance antifouling coatings.