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Hepatic injury is one of the most common digestive system diseases worldwide in clinic. Guanylic acid or guanosine monophosphate (GMP) was an important component of nucleotides, which is mainly in the form of sodium salt (disodium guanylate, GMP-Na 2 ). However, its effect on hepatic injury has not yet been investigated. This study is to investigate the protective effects of GMP-Na 2 on acute hepatic injury induced by carbon tetrachloride (CCl 4 ), and to explore its mechanism. The hepatic injury models of mice and HL-7702 cells were induced by CCl 4 . The alanine transaminase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total antioxidant capacity (T-AOC) were determined by biochemical method. Hematoxylin-eosin staining were used to determine the morphological changes on liver tissue in mice. The mRNA and protein expressions of caspase-3, Bax, and Bcl-2 were detected by RT-PCR and Western blot analysis. Our results show that GMP-Na 2 treatment significantly decreased the activities of ALT and AST, and the levels of MDA as well as increased the levels of SOD, GSH-Px, and T-AOC. Importantly, GMP-Na 2 effectively enhanced the antiapoptosis function by upregulating Bcl-2 expression and downregulating caspase-3 and Bax expressions in vivo and in vitro. Moreover, the histopathological changes of liver tissue were obviously improved after GMP-Na 2 treatment. These findings suggest that GMP-Na 2 has protective effects on hepatic injury, and its mechanisms may be associated with antioxidative stress and antiapoptosis., (© 2019 Institute of Food Technologists®.)