Panax ginseng has been reported to have cancer-preventive properties and, through anti-inflammatory, antioxidant, and pro-apoptotic mechanisms, to influence gene expression. However, the comparison of Korean white ginseng (WG) and red ginseng (RG) in their apoptotic effects and the identification of the selective cellular uptake of the ginsenosides in human breast cancer cells have not yet been fully understood. In the present study, the relative nonpolar and protopanaxadiol (PPD) class ginsenosides exhibited more cytotoxic and efficient cellular uptake on MCF-7 cells compared with the relative polar and protopanaxatriol (PPT) class compounds. PPD class ginsenosides were present in RG in a 2.5 times higher concentration as compared to WG, while PPT class ginsenosides were only present in WG. Thus, RG exerted more potent cytotoxicity than WG against MCF-7 and MDA-MB231 cells. RG also increased the sub-G1 DNA contents of the cell cycle and Annexin V-positive apoptotic bodies undergoing apoptosis through the caspase-3 activation in MCF-7 cells. In addition, RG downregulated the proliferative and anti-apoptotic gene products and potentiated paclitaxel-induced apoptosis in MCF-7 cells. Overall, RG contained a higher concentration of PPD class ginsenosides as compared to WG; the greater cellular uptake of PPD resulted in more substantial antiproliferative activity in human breast cancer cells.