For Hepatocellular carcinoma (HCC) there are no effective treatments thus, the individuation of novel therapeutic approaches and molecular targets are necessary. Small interference RNAs (siRNAs) are small double stranded RNAs able to induce gene silencing and thus represent a potential innovative therapeutic tool. The main impediment in using siRNAs is their high degradation rate in the biological environment. To protect siRNAs, we developed a novel delivery system based on the polymer (α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide-PHEA) derivatized with diethylene triamine (DETA) linked via a polyethylene glycol (PEG) to galactose (GAL) molecules (PDPG). The GAL residue has been introduced to target the Asialo-glycoprotein receptor (ASGPR), overexpressed in HCC cells.