In this paper, we describe the synthesis of water-compatible Molecularly Imprinted Polymer (MIP) microspheres by nanoparticle-stabilized emulsion (Pickering emulsion) polymerization. During the polymerization, the amount of the porogen used not only affected the stability of the Pickering emulsion but also the specific molecular recognition of the obtained MIP microspheres. Under optimized conditions, the MIP microspheres synthesized had a porous and hydrophilic surface. Scanning electron microscopy and fluorescent labeling experiments indicated that the MIP microspheres had particle sizes of 165 ± 38 μm. Selective molecular recognition with the MIP microspheres was studied through equilibrium binding analysis and liquid chromatography experiments under pure aqueous conditions. Using the new MIP microspheres as solid phase extraction (SPE) absorbents, low concentration organic pollutants (β-blockers) were effectively enriched from tap water and easily detected using HPLC-MS analysis.