Saponins are a major active component of Platycodon grandiflorum (P. grandiflorum) and are known to induce apoptosis in metastatic prostate cancer cell lines. However, thus far, no research has been conducted on the anticancer activity of saponins in RC-58T/h/SA#4 primary prostate cancer cells. In this study, we show that the treatment of prostate cancer cells with saponins extracted from P. grandiflorum (SPG) inhibits cell proliferation in a dose-dependent manner. SPG significantly induced apoptotic cell death, resulting in an increase in the sub-G1 apoptotic cell population, apoptotic DNA fragmentation and morphological changes. Pre-treatment with a caspase inhibitor modestly attenuated the SPG-induced increase in the sub-G1 cell population, suggesting that caspases play a role in SPG-induced apoptosis. Moreover, SPG-induced apoptosis was associated with changes in caspase activity, the upregulation of the apoptotic protein, Bax and the downregulation of the anti-apoptotic protein, Bcl-2. Furthermore, the caspase-independent mitochondrial apoptosis factor, apoptosis-inducing factor (AIF) was upregulated following SPG treatment. These findings indicate that SPG exerts its anticancer effects on RC-58T/h/SA#4 primary prostate cancer cells through mitochondrial caspase-dependent and -independent apoptotic pathways.