Abstract: The aim of this study was to explore the protective effects of geniposide against Influenza A(H1N1)pdm09 virus in vitro and in vivo. In vitro, geniposide was administered as a precaution drug, a direct deactivation drug or a treatment drug at different doses. Peramivir was applied as a positive control. The quantitative colorimetric MTT assay was applied to test both the cytotoxicity of geniposide on Madin-Darby Canine Kidney(MDCK)cells and the cytopathogenic effect(CPE)of geniposide on MDCK cells infected by influenza A(H1N1)virus. The viral inhibitory rate of geniposide on NT0901 was also calculated. In vivo, we presented a mouse model of influenza A(H1N1)pdm09 virus infection. Geniposide(5, 10, or 20 mg/kg)or peramivir(30mg/kg)were used as treatment procedures. Lung index and the survival rate were calculated to evaluate the therapeutic effects of geniposide or peramivir on NT0901-infected mice. Haematoxylin and eosin(H&E)stain was used to access the pathological alterations of lung tissues. The study in vitro demonstrated that the TD₅₀(median toxic dose)of geniposide was higher than 1 040 μmol/L. Besides, the EC₅₀(concentration for 50% of maximal effect)of geniposide administered for precaution, direct deactivation and therapy were 91. 90, 96. 25, 87. 68 μmol/L, respectively. These results suggested that geniposide could block the damage of NT0901 on MDCK cells in a dose-dependent manner. The results in vivo showed that geniposide could significantly alleviate the lung index elevation and inflammatory responses in lung tissues induced by NT0901, reduce the mortality of infected mice and extend their survival time. In conclusion, our investigation indicates that geniposide is highly effective in inhibiting cytopathogenic effect and acute lung injury caused by influenza A(H1N1)pdm09 virus. Geniposide may be a potential therapeutic agent for the suppression of influenza virus.