The consumption of mushroom Ganoderma lingzhi (G. lingzhi) is believed to help people fight influenza. However, few scientific studies, particularly in animals, has addressed that. Here, a hot-water extract of G. lingzhi was orally or intranasally administered to mice infected with influenza A virus, following by a 21-day post-infection observation. An in vitro neuraminidase (NA) assay, with four subtypes of NA, was used to assess inhibition. The total content of triterpenoids and carbohydrates in the extract were determined with colorimetric assays. Results showed that intranasal administration of the extract reduced the severe weight loss in infected mice by 55.1%. Oral administration of the extract did not significantly interfere the virus infection. In addition, the extract strongly inhibited NA from influenza virus H1N1 and H5N1. These findings suggest that short-term oral consumption of hot-water extract of G. lingzhi has limited anti-influenza function, which also inform further research for its activity observed.