The design and study on recognition of paracetamol-imprinted polymer for application in quantification of drugs was reported. Base on our previous work, the promising monomer, itaconic acid (IA), was computationally selected rapidly from the virtual library using the interaction energy (ΔE) between a paracetamol (PR) molecule and four monomer molecules as a measure of their interaction. The possible conformation of PR interacting with IA displayed the nature of the interaction between PR and IA; hydrogen bonds (hbs) mainly contribute to this interaction. UV spectra analysis confirmed the occurrence of the hbs interaction between PR and IA at the polymerization stage. The optimal solvents for porogen and eluant were determined by the strength of hbs interaction between PR and the solvents, which were calculated employing density functional theory. The corresponding molecularly imprinted polymers (MIPs) and non-imprinted polymers were prepared and evaluated. The experimental results were consistent with those calculated, which confirmed the validity of the above-related calculation believed to facilitate the selection of monomers and solvents for the synthesis of MIP at molecular level.