Curcumin, an active phenolic agent extract from the Curcuma longa, exhibits excellent anti‐cancer, anti‐inflammation, and neuroprotective effects. We aimed to investigate the anti‐influenza role of curcumin in vitro and in vivo. The effect of curcumin on replication of influenza A virus (IAV) was examined in human lung cancer cell line A549, as well as in a mouse model. Curcumin could inhibit IAV in vitro and alleviate the severity of the disease in the mouse after infection with IAV. The results also indicated that curcumin could trigger expression of Heme oxygenase‐1 in vivo and attenuate IAV‐induced injury to the lung tissue. Furthermore, curcumin could regulate immune response following IAV infection through inhibiting production of local inflammatory cytokines. In addition, curcumin was found to inhibit NF‐κB signalling in macrophages, as well as the subsequent production of cytokines/chemokines responding to IAV infection, by enhancing IκBα and AMPK. Our current study supports the potential of curcumin as a promising treatment against IAV infection, whose effect may be mediated by regulating immune response to prevent injury to the lung tissue.