Heat treatment of Panax ginseng C.A. Meyer at a temperature higher than that applied to the conventional preparation of Korea ginseng has been reported to yield a mixture of saponins with potent cytotoxic properties. In an effort to understand the mechanism of cytotoxicity, we studied the effect of heat-processed crude saponin (H-CS) on the viability, nuclear morphology and apoptotic gene induction of human colorectal carcinoma cells (HCT-15 cells) and human glioma carcinoma cells (U87MG). Treatment of the carcinoma cells with a final concentration of up to 1 mg/mL of H-CS resulted in a dose-dependent decrease in viability. In comparison with non-heatprocessed crude saponin (NH-CS), H-CS exhibited increased cytotoxicity. In addition, H-CS induced more apoptotic nuclear fragments in HCT-15 cells than in NH-CS. An analysis of apoptotic gene expression using quantitative real-time PCR revealed high expression levels of the genes encoding caspase 7, caspase 9, cytochrome C, and Bax at RQ values of 26.87, 17.39, 4.55, and 8.51, respectively. Collectively, our results suggest that H-CS has higher anti-proliferative effects on carcinoma cells by inducing apoptosis of the mitochondrial pathway.