Prostate cancer (CaP) is one of the most prevalent cancers worldwide and the incidence and mortality rates have been rapidly increasing in recent years in Taiwan. Therefore, it is important to development anti-cancer therapy. In this study, KHC-4 was identified from 2-phenyl-4-quionolone derivatives in human prostate cancer cells and as a potential antitumor agent. In this study, we have identified KHC-4 induced apoptosis effects in castration-resistant prostate cancer DU145 cells, and the IC₅₀ value of KHC-4 was 0.1 μM. KHC-4 suppressed the survival signaling p-PI3K and p-Akt and protein levels of Bcl-2 and Bcl-xL, upregulated Bax, cytochrome c and Caspase 8/9 and induced apoptosis by mitochondrial-dependent pathway. In JC-1 assay monitored the loss of membrane potential in KHC-4 treatments. TUNEL assay results showed DNA fragmentation in KHC-4 induced apoptosis. We concluded that KHC-4 exerted anti-tumor effects in DU145 cells by induction of apoptosis.