The catalytic hydrogenation of 2,4-dinitroaniline using a 0.5 wt% Pt/TiO2 catalyst was investigated in a multiphase medium of tetrahydrofuran (THF) pressurized by CO2 at different pressures and at 323 K. When CO2 pressure was increased, the overall rate of hydrogenation simply decreased but the selectivity to the desired product of 4-nitro-1,2-phenylenediamine increased. The noticeable enhancement of the selectivity to 4-nitro-1,2-phenylenediamine can be explained by chemical reactivities of CO2 molecules. In situ high-pressure FTIR and molecular simulations demonstrate that the dissolved CO2 molecules may interact with amino groups of the substrate and weaken the intra-hydrogen bonding between the amino and 2-nitro groups, which results in the change in the relative reactivity of the two nitro groups, yielding the desired product in a higher selectivity. The change in the intra- and inter-molecular interactions between the substrate and CO2 molecules was theoretically examined by DFT calculations.