We report a thermo-responsive molecularly imprinted polymer (MIP) for methotrexate, an anticancer drug. The bulk MIPs were prepared with divinylbenzene as a crosslinker, a variety of functional monomers, and folic acid as a pseudo-template molecule. As a result of simple batch adsorption for methotrexate or folic acid using the MIPs, the selectivity depended on the functional monomers because the functional groups of methotrexate or folic acid were slightly different in each other. After optimization of the preparation conditions, only acidic functional monomers including methacrylic acid (MAA) and sodium p-styrenesulfonate (SS) contributed to the selective adsorption for methotrexate. Furthermore, only the MAA-based MIP provided the thermal responsibility for the binding/release of methotrexate by the suppression of hydrogen bonding at higher temperature, whereas a strong ionic interaction was contributed among broad temperature range in the SS-based MIP. Adsorption isotherms also well supported the differences of the molecular recognition based on the binding constants at low and higher temperatures. Finally, we successfully demonstrated the drug-releasing ability by simple temperature changing with the MAA-based MIP. (C) 2015 Elsevier Inc. All rights reserved.