Abstract: Objective To investigated the therapeutic efficacy and the security of atelocollagen-mediated method combined with cisplatin in prostate cancer through delivering siRNA to cancer xenograft by atelocollagen. Bcl-x_L siRNA, combined with cisplatin(CDDP) and mediated by atelocollagen, in a pregrown solid xenograft derived from prostate cancer. Methods The nude mice with xenograft from PC-3 cells were randomly divided into four treatment groups: two groups for local intraperitoneal tumour injection and the other two groups for systemic intravenous injection. Four siRNAs targeting human Bcl-x_L mRNA were designed and compounded with atelocollagen. Then the compound of Bcl-x_L siRNA/atelocollagen/CDDP or Bcl-x_L siRNA/ CDDP were randomly injected into the treatment groups.At regular intervals,the tumor volumes, liver enzyme and renal function in different groups of mice were measured and evaluated. Results In intratumoral treatment groups,when compared with the injection of Bcl-x_L siRNA, Bcl-x_L expressions in the PC-3 xenograft were effectively downregulated and tumor growth was inhibited by local injection of Bcl-x_L siRNA/atelocollagen (P<0.001).In intravenous treatment groups, Bcl-x_L siRNA/atelocollagen also effectively inhibited tumor growth when compared with the injection of Bcl-x_L siRNA (P<0.001).And there were no significantly statistical differences or severe side effects such as liver or renal damage before or after Bcl-x_L siRNA/atelocollagen in both groups. Conclusion Our results indicate that systemic delivery of siRNA combined with cisplatin via atelocollagen, which specifically targets tumors, is safe and feasible for prostate cancer therapy.