In the process of CO₂ flooding，the mixing system of CO₂ and heavy oil is immiscible. The minimum miscible pressure is higher than formation fracture pressure. The molecular simulation of the mixing system of CO₂ and crude oil was carried out. The effects of the type of downmixing agent，addition amount，temperature and pressure were investigated. The aggregation degree of system of CO₂ molecules and asphaltene molecules in the miscible process was obtained by the radial distribution function，the dispersion state of various molecules was defined，and then the mechanism of action was analyzed. On this basis，PVT phase experiments at high temperature and high pressure were carried out to determine the volume expansion coefficient and CO₂ solubility of the mixed and crude oil after adding different downmixing agent，which verified the molecular simulation results. Finally， trimethyl citrate，benzyl alcohol and ethyl benzoate were optimized to obtain the optimum mixture formula，and then the performance of reducing miscible pressure was evaluated by the fine tube experiment. The results of molecular simulation showed that trimethyl citrate had the most significant reducing miscible pressure effect，which could effectively increase the aggregation degree of CO₂ molecules and reduce the aggregation degree of asphaltene molecules. Under the condition of high pressure（6.90 MPa）and low temperature（308.15 K），the downmixing agent could play its role more effectively. The results of PVT phase experiment showed that 0.23% trimethyl citrate had the best solubilization and swelling effect，which was consistent with the molecular simulation results. The optimum formula of compound downmixing agent was obtained as follows：80% trimethyl citrate，20% ethyl benzoate. The minimum miscible pressure was decreased by 21.47%，meanwhile the CO₂ solubility and oil recovery efficiency were improved by adding 0.23% compound downmixing agent to the crude oil-CO₂ system. Containing oleophilic hydrocarbon groups and CO₂ -philic ester groups，the downmixing agent could not only bind with polar molecules in crude oil system，break up the aggregates of each asphalt molecule，but also adsorb on the interface of crude oil and CO₂ under the action of both parent properties，reduce the interfacial tension between crude oil and CO₂ ，and then reduce the minimum miscible pressure.