Ethnopharmacological relevance: Fu Rong Ye (FRY), the leaf of Hibiscus mutabilis L., is a Chinese medicinal herb used to treat coughs and respiratory diseases. FRY is the major herbal component of the patent medicine Fupo Ganmao Granules for treating common cold. However, its anti-influenza active components and mechanism were not identified.Aim: Here, we aim to a) isolate the anti-influenza phytochemicals from FRY extract and b) explore its anti-flu mechanism.Material and methods: Bioassay guided isolation was performed to get anti-influenza virus components. Influenza virus infected cells and mouse model were employed for efficacy evaluation. Results: Using bioassay-guided isolation, the flavonoid tiliroside was obtained, which inhibited four IAV strains in MDCK cells with EC50 ranging from 3.87 to 27.61 mu M by suppressing the viral ribonucleoprotein activity. Tiliroside also significantly downregulated the expression of cytokines/chemokines in A549 cells, and protected 50% of PR8-infected BALB/c mice from death and at 800 mg/kg/day, improved lung edema conditions.Conclusion: Tiliroside is effective for influenza virus infection treatment and promising for further drug devel-opment. This study is the first to demonstrate that tiliroside in FRY acts against influenza virus.