Successful gene therapy depends on efficient delivery of DNA to cells. Stealth liposomes are well characterized for the delivery of cancer drugs and have demonstrated numerous desirable attributes for a delivery system, including increased circulation time in vivo, ability to protect the encapsulated contents and successful delivery of the drug load to the cells of interest. In our lab we have previously demonstrated that delivery can be further improved by incorporating into the liposomes a peptide sequence which targets integrin α5β1 expressed on colon cancer cells. Here we describe these targeted stealth liposomes as carriers for the delivery of poly-L-lysine-condensed plasmid DNA (pDNA). In vivo studies in mice with intrahepatic CT26 tumors showed successful delivery and expression of encapsulated pDNA. Further, when compared with polyethyleneimine (PEI)-mediated delivery and hydrodynamic injection of naked pDNA, these liposomes were substantially more efficient on a per μg basis. In vitro studies have confirmed that α5β1 targeting improves delivery over traditional stealth liposomes. Taken together these results indicate that this system may be a viable method for specific, efficient in vivo delivery of DNA to cancer cells.