Aim: The present study evaluates the feasibility of the incorporation of palmitoylated arabinogalactan in solid lipid nanoparticles and its potential as a hepatospecific targeting ligand. Background: Human hepatocellular carcinoma (HCC) is a neoplasm presenting low survival and higher incidence, due to difficulties in the treatment modalities to effectively place cancer therapeu-tics at the site. Targeting asialoglycoprotein receptors on the surface of hepatocytes employing lipid nanoparticles, and liposomes presents opportunities for improvement in therapy. Objective: The objective of the present investigation was to fabricate and evaluate the potential of palmitoylated arabinogalactan (PAG) incorporated SLNs to target asialoglycoprotein receptors. Methods: Daunorubicin-loaded targeted SLNs prepared by ultrasound dispersion method were evaluated for in vitro release and in vitro cytotoxicity. Lipids, surfactants, and biocompatible sol-vents were screened for SLN formation and optimization was done using 22 factorial designs. Results: The particle size for formulations was below 200 nm with a unimodal distribution. Differ-ential scanning calorimetry analysis revealed the interaction of lipids with other components charac-terized by a shift in lipid melting endotherm. Daunorubicin-loaded PAG SLNs released a signifi-cantly higher amount of daunorubicin at pH 5.5 as compared to pH 7.4, providing an advantage for targeted tumor therapy. In vitro cytotoxicity studies showed that daunorubicin depicted a dose-dependent reduction in viability in all cell lines treated with formulation as well as free drug. Conclusion: SLNs showed enhancement in intracellular uptake of daunorubicin thereby establish-ing their potential in improved treatment of HCC and warrant further in vivo investigations.