Abstract: This study is to investigate the effects of the c-Myc inhibitor 10058-F4 in acute liver injury induced by lipopolysaccharide（LPS） and D-galactosamine（D-Gal） and its underlying mechanism. 32 male BALB/c mice（Mus musculus） were randomly divided into four groups: control group, 10058-F4 group, LPS/D-Gal group and 10058-F4+ LPS/D-Gal group. Acute liver injury was induced by intraperitoneal injection of LPS/D-Gal, and 10058-F4 was injected intraperitoneally 0.5 h prior LPS/D-Gal. The mice were sacrificed at 1.5 h post LPS/D-Gal exposure, and the mRNA level of tumor necrosis factor-α（TNF-α） in liver and the level of TNF-α in serum were determined by quantitative real-time PCR and ELISA, respectively. Another 32 mice were prepared and undergone the same above-mentioned procedure, then sacrificed at 6 h post LPS/D-Gal exposure, and the levels of transaminases and interleukin-6（IL-6） in serum were determined. The mRNA level of IL-6 and the activities of cysteinyl aspartate specific proteinase（Caspase）, including Caspase-3, Caspase-8 and Caspase-9 in li-ver were determined. In addition, hematoxylin-eosin（HE） staining was used to observe the histopathological changes and hepatocellular apoptosis was observed by TUNEL assay. The results showed that treatment with the c-Myc inhibitor 10058-F4 in LPS/D-Gal-exposed mice significantly decreased the levels of serum alanine aminotransferase（ALT） and aspartate aminotransferase（AST）, decreased the mRNA levels of TNF-α and IL-6 in liver, and reduced the serum levels of TNF-α and IL-6. The 10058-F4-treatment also suppressed the acti-vation of Caspase-3, Caspase-8 and Caspase-9, reduced the count of TUNEL-positive hepatocytes and alleviated the degree of liver lesions. In conclusion, the c-Myc inhibitor 10058-F4 alleviated LPS/D-Gal-induced acute liver injury, these protective benefits might be associated with the compromised inflammation and suppressed apoptosis.