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. The gene discussed is EPHA2; the disease is Familial prostate cancer.