Molecular modeling of CO₂-polymer system was established to study the molecular behaviors and intermolecular interaction of copolymers in supercritical carbon dioxide (SC-CO₂) by all-atom molecular dynamics (MD) simulation. According to the simulation results, the correlations of the intermolecular interaction with the molecular structure and composition were explored. The effects of intermolecular interactions on the copolymer properties in SC-CO₂ were identified. A series of copolymers were synthesized with CO₂-philic monomer 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-Heptadecafluorodecyl acrylate (HFDA) and CO₂-phobic monomer vinyl n-Octanoate (VOc), vinyl acetate (VAc), vinyl pivalate (VPi), respectively. The solubility and viscosification of the copolymers in SC-CO₂ were evaluated by cloud point pressure and relative viscosity measurements. It was found that P(HFDA_0.49-co-VAc_0.51), which is the most effective thickener among the copolymers, could enhance the viscosity of SC-CO₂ by 62 times at 5 wt%. It was suggested that the thickening capability of the copolymers in SC-CO₂ may originate from intermolecular cross-links generated by associative groups. Combining the molecular simulation and experiment results, the structure-activity relationships of the copolymers in SC-CO₂ were revealed. It is believed that the molecular simulation aided design method for the SC-CO₂ copolymer thickener is reliable.