Cr(VI) is a representative heavy metal which has significant toxicity to biological organisms. Ion-imprinted polymers (IIPs) have been recognized as effective adsorbents to remove Cr(VI) from environment. Among them, imidazole derivatives are expected to serve as potential monomers for Cr(VI)-IIPs, but the binding mechanisms of monomers with Cr(VI) remain unclear, which makes Cr(VI)-IIPs design having rare sound theory to be guideline. In this work, the suitable functional monomer of Cr2O72--IIPs was screened among five imidazole derivatives (adenine, cytosine, uric acid, l-histidine, 1-methacryloyl imidazole) with a target-monomer binding affinity guide strategy, and the optimal self-assembling conditions were investigated using theoretical calculations and experimental methods. Adenine exhibited the highest potential among the five candidate monomers, followed by cytosine. The optimal ratio of target and monomer was determined to be 2:3. Furthermore, a 5:5 mixture of ethanol and cyclohexane was identified as the most suitable solvent for the pre-polymerization environment, while epichlorohydrin acted as the most appropriate crosslinker. Additionally, the binding nature of non-covalent interaction between target and monomer was identified to be electrostatic-dominated hydrogen bonding. These mechanistic insights provide valuable theoretical support for the rational design of Cr2O72--IIPs, which are significant for IIPs development as adsorbents for contaminants detection and removal from environment.