Hepatocellular carcinoma (HCC) is the most common cancer and ranks third in the world in terms of cancer- related mortality. Chemotherapy is a clinical treatment for HCC. However, most anticancer medications exhibit significant toxic effects and reduced selectivity, which induce systemic toxicity. However, the targeted delivery of the drug to the liver was achieved successfully. In the current study, we designed a nanocomplex of chitosan nanoparticles loaded with silymarin that was galactosylated to target the asialoglycoprotein receptor, which is present in liver cells. The adjusted nanocomplex and its components were characterized using various techniques. An in vitro release study was performed. The study performed bioassays against HepG2 cell lines for cytotoxicity, ROS generation, flow cytometry to detect cell cycle analysis, and levels of the apoptotic markers TGF-1, Bcl-2, Cytochrome c, Caspase-3, Caspase-8, and Caspase-9. According to our results, targeted Silymarin significantly increased the expression of pro- apoptotic proteins such as p53 and caspase-3 and reduced anti-apoptotic proteins such as Bcl-2. Taken together, our results propose that the prepared nanocomplex might signify a promising tumor-targeting drug delivery system that can carry anticancer agents in a precise way to enforce HCC outcomes in the future.