MOV10 has emerged as an important host antiviral factor. MOV10 not only inhibits various viruses including human immunodeficiency virus type 1, hepatitis C virus and vesicular stomatitis virus, it also restricts the activity of retroelements LINE-1, Alu, SVA and IAP. Here we report that MOV10 suppresses influenza A virus infection through interacting with viral nucleoprotein, sequestering viral RNP in the cytoplasm and causing the degradation of viral vRNA. This antiviral activity of MOV10 depends on the integrity of P-bodies. We also found that the antiviral activity of MOV10 is partially countered by viral NS1 protein that interferes with the interaction of MOV10 with viral nucleoprotein and causes MOV10 degradation through the lysosomal pathway. Moreover, NS1 defective IAV is more susceptible to MOV10 restriction. Our data not only expand the antiviral spectrum of MOV10, but more importantly reveal the NS1 protein as the first viral antagonist of MOV10.