Abstract: Disclosed herein are compositions and methods for targeted treatment of liver cancers with Paclitaxel and miR-122. The disclosed composition comprises RNA nanostructure conjugated to a hepatocyte targeting ligand, paclitaxel, and miR-122 for use in intracellular drug delivery to liver cancer cells. The RNA nanoparticle can involve three or more self-assembled synthetic RNA oligonucleotides that form a central core domain and at least three double-stranded arms arranged around the core domain and extending away from the central core domain.