Influenza A viruses (IAV) still pose a threat to animals and humans. Currently, M2 protein ion channel inhibitors and neuraminidase inhibitors are the two main drugs for treating IAV infections by interrupting virus assembly or release respectively, but the emergence of viral resistance was a concern for their long term uses. In this study, the inhibition effect of alpha-lipoic acid (α-LA) on IAV propagation has been evaluated in vitro. The results showed that α-LA inhibited IAV replication in MDCK cells at 2mM, and also reduced nucleus translocation of nuclear factor κB (NF-κB) p65 at the concentration above 1mM. Additionally, it was found that caspase-3 activity was remarkably inhibited and type I interferons (IFNs) were up-regulated following α-LA treatment. This study indicated that α-LA might be a potential anti-influenza virus agent worthy of further investigations.