In our previous work, poly(butyl acrylate) (PBA) latex microspheres (LMs) were embedded within hydrogels to enhance their mechanical strength. Herein, acrylonitrile (AN) components were added to the latex system to prepare novel poly(butyl acrylate-acrylonitrile) (P(BA-AN)) LMs. LMs were able to adsorb hydrophobic hexadecyl methacrylate (HMA) due to hydrophobic interactions, stabilized by using sodium dodecyl sulfate as a surfactants. The HMA could occur radical copolymerization with acrylamide (AAm) under the redox initiators to form P(HMA-AAm)-P(BA-AN) hydrogels. The intra and interchain non-permanent binding could be promoted in P(BA-AN) LMs due to the dipole-dipole interactions of -CN groups from acrylonitrile. As a result, P(BA-AN) LMs were utilized to fabricate tough hydrogels as crosslinking centers for hydrophobic association. The mechanical properties of the hydrogels exhibited a fracture stress of 775 KPa, an ultrastretchable strain of 3600% and a fracture energy of approximately 7600 KJ/m3. This innovative design strategy for LMs capable of strong physicochemical interactions, including electrostatic and hydrogen-bond interactions and coordination effects, may open a novel direction for the production of tough hydrogels.