Abstract: Purinergic receptors are widely distributed in the human body and participate in such various biological processes as intracellular energy homeostasis, nucleotide synthesis and chemical signal transduction. Current research indicates that purinergic receptors are closely associated with the development of metabolic syndrome-related non-alcoholic fatty liver disease, alcoholic liver disease, drug-induced liver injury, liver fibrosis, hepatocellular carcinoma and a range of hepatic inflammatory disorders. Under conditions of inflammation or injury, cells release nucleotides as danger signals. Endogenous nucleotides regulate cellular physiological responses by binding to purinergic receptors, which plays a critical role in maintaining liver function. This article reviews the biological functions of different purinergic receptors in hepatic homeostasis and the current status of drug development targeting purinergic receptors, and highlights their roles in liver diseases, aiming to provide insights for elucidating the pathogenesis of liver diseases and developing novel clinical therapeutic strategies.