Limitations of the current vaccines and antivirals against influenza A virus pandemic underscores the urgent need for developing a novel anti-influenza strategies. RNA interference (RNAi) induced by small interfering RNA (siRNA) has become a powerful new means to inhibit viral infection in a gene-specific manner. However, the efficacy of the siRNA delivery platform and the relatively high cost of administration hindered wide application of siRNA. In this study, we developed a microRNA-30 (miR-30) based lentivirus delivery system by embedding a synthetic shRNA stem into the context of endogenous precursor of miRNA-30 (shRNAmir) to express the silencer of influenza gene. We showed that the miRNA based lentivirus vector was able to express and process a single NP targeting shRNAmir, which could potently inhibit IAV replication. We further showed that miRNA based lentivirus vector carrying tandemly linked NP and PB1 shRNAmirs could express and process double shRNAmirs. Despite of the relative low levels of NP and PB1 miRNAs produced in the stably transduced cells, the combination of two miRNAs exerted a great degree of inhibition on influenza infection. Given the advantage of combinatorial RNAi in preventing emergence of mutant virus, miRNA based lentiviral vectors are valuable tools for anitiviral activities. To our knowledge, this is the first study demonstrating that miRNA based RNAi strategy can be applied for a better control for influenza virus infection.