A novel amphiphilic hydrogel based on poly(2-methyl-2-oxazoline)-b-poly(dimethyl siloxane) (PMeOx–PDMS) block copolymer was developed. First of all, PMeOx–PDMS macromonomer was synthesized by coupling mono-hydroxylated PMeOx with PDMS followed by end-capping with methacrylate group. The structures of each step were characterized by NMR and titration. After that, silicone hydrogels were prepared by UV-initiated copolymerization of PMeOx–PDMS macromonomer with monomers such as 2-hydroxyethyl methacrylate in the presence of a crosslinker. Measurements of the hydrogels' water contact angle, equilibrium water content, and tensile properties showed that the hydrogels possessed better hydrophilic surface, higher water content, and better ion permeability with the increase of the content of the macromonomer PMeOx–PDMS. Meanwhile, the tensile strength and Young's modulus of the hydrogels decreased slightly. Protein adsorption tests showed that the hydrogels had strong antifouling ability after the incorporation of PMeOx. This newly described hydrogel demonstrated attractive properties to serve as ophthalmic biomaterial. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39867.