Understanding the host response to influenza A virus infection is essential for developing intervention approaches. We show that infection of human alveolar epithelial cells and human bronchial epithelial cells with influenza A for 3h resulted in down-regulation of host hsa-miRNA-548an (miRNA-548an) which triggered the overexpression of influenza non-structural-1A binding protein (IVNS1ABP, herein referred to as NS1ABP). Reduced NS1ABP mRNA and NS1ABP protein expression after transfection of miRNA-548an mimic or increased NS1ABP mRNA and NS1ABP protein expression after transfection of miRNA-548an inhibitor provided evidence that miRNA-548an is involved in the regulation of NS1ABP. Transfection of cells with inhibitor led to reduced apoptosis of infected cells while transfection of mimic led to increased apoptosis and reduced influenza copy number suggesting that NS1ABP has a role in viral maintenance. Thus, miRNA-548an may be an important target in controlling the early stage infection of influenza A.