Non-covalent imprinting polymerization was adopted to fabricate a novel molecularly imprinted polymer (MIP) for the targeted delivery of Irinotecan. The optimized condition to obtain a MIP with the highest binding efficiency was investigated by using different proportions of monomer to cross-linker. To overcome the drawbacks of conventional drug delivery systems, two main strategies in the preparation of the carrier were applied. Metformin as a non-hazardous material, with potential anti-cancer and targeted delivery properties, was used to fabricate the monomer. Moreover, the surface of the carrier was modified by serotonin (5-hydroxytryptamine). To improve the cellular uptake, prolong the circulation time, and to provide an appropriate accumulation of the drug at the tumor site, uniform, and nanoparticles were fabricated via mini-emulsion polymerization route. The structure of the prepared monomer was characterized using FTIR, 1HNMR, 13CNMR, and mass spectroscopy. The adsorption isotherm of the Irinotecan-MIP nanoparticles was investigated. Bio-distribution assay results revealed a suitable distribution of carrier nanoparticles in mice bodies. A controlled release profile with a maximum release of 83% in more acidic condition, was achieved for the designed formulation. According to all the above functions, it is believed that this study suggests a novel nano-carrier for the targeted delivery of Irinotecan.