Molecularly imprinted polymers (MIPs) with selective recognition properties for zearalenone (ZON), an estrogenic mycotoxin, and structurally related compounds have been prepared using the non-covalent imprinting approach. A rationally designed ZON analogue, cyclododecyl 2,4-dihydroxybenzoate (CDHB), that exhibits resemblance to ZON in terms of size, shape and functionality has been synthesized and used as template for MIP preparation instead of the natural toxin. Several functional monomers have been evaluated to maximize the interactions with the template molecule during the polymerization process. The polymer material prepared with 1-allylpiperazine (1-ALPP) as functional monomer, trimethyl trimethacrylate (TRIM) as cross-linker and acetonitrile as porogen (in a 1:4:20 molar ratio) displayed superior binding capacities than any other of the MIPs tested. Selectivity of this material for ZON and structurally related and non-related compounds has been evaluated using it as stationary phase in liquid chromatography. Our results demonstrate that the imprinted polymer shows significant affinity in the porogenic solvent for the template mimic (CDHB) as well as for the ZON and other related target metabolites in food samples, dramatically improving the performance of previously reported MIPs for ZON recognition. Therefore, MIPs can be an excellent alternative for clean-up and preconcentration of the mycotoxin in contaminated food samples.