CO2-assisted hydrothermal reactions were performed for the conversion of intact ginsenosides to the more bioactive ginsenosides, (S)-Rg3, (R)-Rg3, Rk1, and RgS. The yields of the transformed ginsenosides and anticancer activities were compared for the three processes: conventional steaming, hydrothermal processing, and CO2-assisted hydrothermal processing. In the CO2-assisted hydrothermal process, approximately 2 times higher yields of transformed ginsenosides were obtained within 30 min compared to the steaming process, which requires autoclaving for 3 h, at the same temperature of 120 degrees C. These improvements were attributed to the homogeneous reaction condition and the in-situ generation of carbonic acid. Moreover, the CO2-assisted hydrothermally processed ginseng showed the highest antiproliferative effects on HT 1080 and MDA-MB-231 cells by stimulating apoptosis. Due to the higher yields of transformed ginsenosides, similar antiproliferative effects could be obtained using only 10-20% of the amounts used in previous studies.