Previous studies have demonstrated the key regulatory roles played by microRNAs (miRNAs) in influenza virus-host interactions. To gain more insight into the contribution of miRNAs to the host immune response, spleen tissues from mice infected with A/Swine/GD/2/12 (H1N1) virus were harvested 5 days postinfection, and miRNA deep sequencing was performed. The results showed that 50 miRNAs were modulated. Interestingly, pathway analysis of miRNAs and targets showed that upregulated miR-124-3p interacts with innate immune-related pathways such as the Toll-like receptor pathway, RIG-I-like receptor signaling pathway, NOD-like receptor signaling pathway and JAK-STAT signaling pathway, and this might play a major role in the anti-inflammatory response. Further understanding of the roles played by these miRNAs in influenza virus infection will provide new insights into host-pathogen interactions.