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Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related deaths. In the United States, the incidence of HCC has almost tripled during the past two decades and HCC has become one of the fastest growing cancers. While surgical removal of tumor tissues is an effective approach to protect relatively healthy liver tissue, it is only applicable to a small subset of HCC patients with specific pathological conditions, such as confined tumor mass without portal hypertension. Therefore, there is an urgent need to develop novel therapeutic strategies to treat this deadly disease. Systemic tumor-targeted gene delivery is attracting increasing attention as a promising alternative to conventional therapeutic strategies. At this purpose a large number of viral and non-viral vectors have been studied and applied as systems of stable transfection with low toxicity. Although cationic polymers and liposome are promising systems, solid lipid nanoparticles (SLN) have been recently proved to be a really useful vehicle for gene therapy [1,2]. The aim of this work was to design and to obtain cationic SLNs capable of forming complexes with siRNA and DNA plasmid for the treatment of HCC. The physical binding between cSLN and nucleic acids was confirmed by the study of complexes’ zeta potential values that became more positive as higher was the amount of cSLN and via the electrophoretic mobility of the samples in agarose gel 0.8%. Transfection studies on different tumor cell line are in progress.