Acute liver injury is a serious threat to human health. Complementary therapy including a traditional Chinese herb has been used for the prevention and treatment of liver injuries. Schisandrae sphenantherae fructus (Schisandra) is the mature dry fruit of Schisandra sphenanthera Rehd. et Wils. Wuzhi capsule, a preparation containing Schisandra and its main component anwulignan, is used to treat hepatitis and hepatic insufficiency caused by viruses and drugs in the clinic. However, to date, there has been little study to reveal the effect of anwulignan in the protection of the liver. Therefore, in this study, we hypothesized that anwulignan could protect carbon tetrachloride (CCl4)-induced acute liver injury in mice. Anwulignan was shown to reduce significantly the liver index, decrease liver histopathological injury, decrease the serum level of aspartate aminotransferase and alanine aminotransferase, increase the activities of superoxide dismutase (SOD) and glutathione peroxidase, reduce liver malondialdehyde content, and downregulate the expression levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α in the liver tissue, as well as the protein expression levels of receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, and phosphorylated mixed lineage kinase domain-like protein. All these results suggest that anwulignan can alleviate the CCl4-induced acute liver injury in mice, which may be related to its antioxidant, anti-inflammation, and inhibition of liver cell necroptosis effects.