Abstract: Compound houttuynia mixture belongs to OTC class A medicine, which is made from Houttuynia cordata, Scutellaria baicalensis, Radix Isatidis, Forsythia, and Lonicera. As a kind of compound preparation of traditional Chinese medicine, houttuynia cordata mixture has extensive pharmacological effects, for example, clearing away heat and detoxifying, thus it is used for the sore throat, acute pharyngitis, and tonsillitis with wind-heat syndrome. In this study, the antiviral activity against influenza viruses and the primary mechanism of compound houttuynia mixture was evaluated. The antiviral effect of compound houttuynia mixture was determined by cytopathic effects (CPE), Western blot, quantitive reverse transcription PCR (qRT-PCR), and virus titer assays. The effect of houttuynia mixture on the replication cycle of influenza virus was evaluated by time-of-addition assay. In conclusion, the results showed that the compound houttuynia mixture had a broad-spectrum effect against influenza virus, including the international common influenza virus strains, the drug-resistant strains and the highly pathogenic avian influenza viruses H5N1 and H7N9. It mainly impairs the early stage of the viral replication.