C-H-O interaction of acetone and deuterium oxide has been probed by high pressure. High-pressure study provides the first experimental evidence for the enhancement of hydrophobic hydration of acetone as its aqueous solution was compressed to high-pressure ices. Based on the results, we conclude that the C-H-O interaction may be a distinct possibility to understand the origin of the spectral feature located at similar to 2950 cm(-1), being sensitive to concentration and pressure dependence. Ab initio calculation results, forecasting the frequency red shift of the C-H stretching vibration as C-H-O is interacted via hydrogen bonding, are discussed. This study demonstrates that high pressure can be used as a valuable means of triggering and investigating C-H-O hydrogen-bonding interaction.