OBJECTIVE: To evaluate the effects of p21 small activating RNA (saRNA) in combination with PC-3 on the apoptosis of LNCaP cells. STUDY DESIGN: LNCaP cells were collected 24 hours after the addition of PC-3 and 72 hours after being transfected with p21 saRNA. The MTT assay was used to determine the inhibition rate of cell viability. After Annexin-V-PI staining, flow cytometry was used to analyze the effect on apoptosis and cell cycles. Western blot was used to detect the changes of p21 protein expression. RESULTS: p21 saRNA in combination with PC-3 significantly inhibited the viability of LNCaP cells, promoted apoptosis, and retarded the cell cycle to phase G0/G1 as compared with the results of p21 saRNA transfection or PC-3 for treatment alone. It was demonstrated by Western blot that this combination facilitated apoptosis and retarded cell cycle by activating the p21 network. CONCLUSION: p21 saRNA in combination with PC-3 can be used to induce LNCaP cell apoptosis and may become a tool for treating hormone-independent prostate cancer. © Science Printers and Publishers, Inc.