Asialoglycoprotein receptor (ASGPR) was specifically expressed by hepatocytes, which could recognize and bind asialoglycoprotein, galactose (Gal), galactosamine, N-acetylgalactosamine (GalNAc), etc. with high affinity. In a receptor-mediated-endocytosis (RME) manner, various molecules could be delivered into hepatocytes effectively. In this review, we firstly introduced the discovery, structure, function, expression pattern and endocytosis properties of ASGPR. Then the influence factors of ligand/receptor interaction and RME, including ligand species, valence, orientation and particle size, were analyzed. In addition, studies on ASGPR-mediated drug delivery in the past decades were reviewed. More importantly, progress in GalNAc-conjugation or -modification technologies employed in liver-targeted transportation of siRNA, antisense and antagomir were summarized.