Current strategies to treat androgen-independent prostate cancer are associated with a number of challenges and are not yet curative. Matrine is a naturally occurring alkaloid extracted from the Chinese herb Sophora flavescens. Matrine has shown anti-proliferative properties in a number of types of cancer, including breast, gastric, lung and pancreatic tumors. Matrine was also found to promote apoptosis and inhibit invasion of cancer cells. We evaluated the antitumor effects of matrine on androgen-independent PC-3 prostate cancer cells. The effects of matrine on cell cycle progression and apoptosis of PC-3 cells were tested. Matrine-treated PC-3 cells underwent G0/G1 cell cycle arrest. There was a significant reduction in the number of S phase and G2/M phase cells in the treated group when compared to untreated cells. Flow cytometry, as well as Annexin-V/PI staining, showed a significant, dose-dependent increase in the number of early, as well as late, stage apoptotic cells in matrine-treated cells compared to untreated cells. There was also an increase in the number of necrotic cells in the matrine-treated group when compared to untreated cells. Matrine treatment resulted in increased levels of caspase-3 and Bax and decreased levels of Bcl-2. Our data suggest that matrine inhibits the proliferation of androgen-independent prostate cancer cells by causing G0/G1 cell cycle arrest and promoting apoptosis. Matrine‑induced apoptosis was mediated by downregulation of Bcl-2/Bax ratios and upregulation of caspase-3 levels. Based on our data, we suggest that matrine may be a novel addition to the current arsenal of strategies used to treat androgen-independent prostate cancer.