Abstract: We have developed a tumor-targeted LPD formulation (liposome-polycation-DNA complex) for siRNA. With surface modification, the targeted, PEGylated LPD increased the delivery efficiency by four-fold and the gene-silencing effect by two- to three-fold. Downregulation of survivin in human lung cancer cells by targeted LPD induced 90% of apoptosis and sensitized the cells to cisplatin by four-fold. PEGylated LPD formulation also significantly improved the tumor localization of siRNA in the NCI-H460 human lung cancer xenograft model. The tumor appeared to be the major uptake organ for siRNA formulated in surface-modified LPD. Our encouraging results indicate that surface-modified LPD may be a potent carrier for RNAi-based tumor therapy.