Lack of specificity towards cancer cells is a major drawback of most chemotherapeutic agents. The use of selective drug delivery systems capable of targeting cancer cells is a valuable perspective to overcome the serious adverse effects often associated with conventional treatments. In this frame, N-acetylgalactosamine (GalNAc)-functionalized G-quadruplex-forming oligonucleotides represent promising delivery systems due to their ability to selectively recognize the asialoglycoprotein receptor (ASGPR) overexpressed on the surface of hepatocellular carcinoma cells. Here, we investigated the interaction of two small molecules, previously proved to induce cancer cell death by selective recognition of cancer-related G-quadruplexes, i.e., the trifunctionalized naphthalene diimide NDI-5 and the alkaloid Dicentrine, with a set of chemically different GalNAc-functionalized G-quadruplexes, some of them derivatized with floxuridine units, here chosen as suitable drug carriers. Several biophysical techniques, such as fluorescence spectroscopy, circular dichroism and gel electrophoresis, were exploited to characterize these systems and evaluate their stability in pseudo-physiological solutions. In addition, the cytotoxicity of the best ligand/GalNAc-functionalized G-quadruplex complexes was evaluated in hepatic and cervical cancer cell lines, using a normal cell line as control, to assess the selective anticancer effects of our delivered drugs and, more in detail, their selectivity of action against the hepatic cancer cells. Taken together, the obtained results demonstrated the high potency and synergistic effects of ligand/GalNAc-functionalized G-quadruplex complexes as effective and selective anticancer drugs delivery systems, especially for the treatment of hepatocellular carcinoma.