The invention belongs to the technical field of animal model construction, and discloses application of lipopolysaccharide-mediated severe liver injury and a construction method of an animal model. The method comprises the following steps: (1) establishing a mouse model with severe mouse liver injury through different doses of carbon tetrachloride; (2) using different doses of lipopolysaccharide for inducing liver injury and determining critical doses (less than 0.5 mg/kg, a contrast model) which do not cause mouse liver injury under normal physiological conditions. And (3) constructing a model for severe mouse liver injury induced by carbon tetrachloride mediated by 0.1 mg/kg lipopolysaccharide and an evaluation system for severe liver injury. The method comprises the following steps: inducing a mouse for 24 hours by using carbon tetrachloride, and controlling by using a solvent olive oil; using lipopolysaccharide to induce mice, and controlling by using PBS; intervening a model mouse induced by 1ml/kg of carbon tetrachloride through 0.1 mg/kg of lipopolysaccharide. The invention lays an experimental foundation for researching the application and related mechanisms of the severe liver injury of the lipopolysaccharide-mediated animal model.