A versatile strategy, based on the use of an amphiphilic copolymer as a macromonomer, was developed for the preparation of a fully synthetic MIP (molecularly imprinted polymer) sensor for protein recognition. A UV-crosslinkable copolymer poly(DMA-co-HEA-co-St) (UPDHS) was designed and synthesized to assemble with the template protein in aqueous solution, resulting in the fabrication of protein imprinted polymeric nanoparticles. Linear macromolecular chains were used to protect the structural integrity of the protein, through which a 3D structure was formed around the protein molecule to generate recognition cavities. Then the nanoparticles were immobilized on the cleaned surface of a transducer as an MIP sensing platform. The resultant MIP coating was then irradiated via ultraviolet light to ensure that the recognition cavities were stable after UV curing. After protein extraction, recognition cavities complementary to the protein molecule in shape, size and chemical functionality were formed in the platform, which could then selectively rebind to the template in a mixture of closely related compounds. The sensor exhibited satisfactory selectivity, a wide linear range from 10 to 10 mg mL, and a comparatively lower detection limit for protein detection. This strategy offers a new and straightforward method for the synthesis of receptors for label-free and cost-efficient protein recognition. This is one of the most effective and versatile strategies for the preparation of high-performance protein recognition devices based on a fully synthetic MIP.