Swine are reservoirs for anthropogenic/zoonotic influenza viruses, and the prevalence and repeated introduction of the 2009 H1N1 pandemic influenza virus (pdm/09) into pigs raises the possibility of generating novel swine influenza viruses with the potential to infect humans. However, studies aiming to identify miRNAs involved in the transfer of novel swine influenza virus infection to human cells are rare. In this investigation, from the view of small RNA, microarrays and high-throughput sequencing were used to detect differentially expressed miRNAs and mRNAs after human lung epithelial cells were infected with the following three stains of influenza viruses: a novel H3N2 swine influenza virus reassorted with pdm/09 fragments, pdm/09 and classical swine influenza virus. A miRNA-mRNA interaction map was generated to show the correlation between miRNAs related to infection by the viruses with human infective potential/capability. The expression of 4 miRNAs (hsa-miR-96-5p, hsa-miR-140-5p, hsa-miR-30a-3p and hsa-miR-582-5p) and 5 relevant mRNAs (RCC1, ERVFRD-1, RANBP1, SCARB2 and RPS29) was determined. The integration analysis indicated that these candidates have rarely been reported to be associated with influenza virus. Focusing on miRNA expression changes could reveal novel reassortant viruses with human infective potential that may provide insight into future pandemics.