In summary, we successfully developed a novel DDAB-cSLN/siRNA complex targeting EphA2, which (i) has small particle size and size distribution, (ii) is biocompatible with normal prostate epithelial cell lines, (iii) protects siRNA against nucleases, (iv) shows high cellular uptake, (v) provides gene silencing as effective as the commercial transfection agent Dharmafect-2 in prostate cancer cell models in vitro. This evidence concerns the gene EPHA2 and prostate carcinoma.