a b s t r a c tLittle is known about the role of microRNA during influenza A virus (IAV) infection. We observed that NIK 3 0 UTR luciferase activity was elevated during IAV infection. Further studies demonstrated that miR-302c reduced NIK expression, resulting in the reduction of IFNb mRNA expression. We found that miR-302c prevented the translocation of NF-jB from the cytosol to the nucleus. Furthermore, IAV infection downregulated miR-302c expression, leading to the activation of IFNb expression and the inhibition of viral replication. Compared to miR-302c, miR-520e cannot promote viral replication and production, although the two microRNAs target the same site of the NIK 3 0 UTR. Collectively, our work defines a novel signaling pathway implicated in the control of IFNb mRNA expression during IAV infection.