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Ligand‐targeted drug delivery (LTDD) has emerged as an attractive option in the field of oligonucleotide drugs following the great success of N‐acetylgalactosamine (GalNAc)–conjugated siRNA and antisense oligonucleotides. GalNAc is a well‐known ligand of the asialoglycoprotein receptor (ASGPR), and is classified as a C‐type lectin associated with the metabolism of desialylated glycoproteins. This article describes the synthesis of a non‐nucleosidic monovalent GalNAc phosphoramidite—a useful reagent for facilitating the conjugation of GalNAc epitopes into oligonucleotides using DNA synthesizers—together with some important caveats. The monomeric GalNAc consists of three parts: (1) a GalNAc moiety, (2) a linker moiety, and (3) a trans‐4‐hydroxyprolinol (tHP) branch point. The GalNAc moiety and the tHP moiety are coupled via a condensation reaction to prepare the monovalent GalNAc phosphoramidite. © 2019 by John Wiley & Sons, Inc. Basic Protocol 1: Synthesis of N‐acetylgalactosamine ligand Basic Protocol 2: Preparation of trans‐4‐hydroxyprolinol building block Basic Protocol 3: Preparation of GalNAc phosphoramidite