Enterovirus 71 (EV71) is the major pathogen causing severe neurological complications, hand, foot, and mouth disease. The intestinal mucosal immune system has a complete immune response and immune regulation mechanism, consisting of densely arranged monolayer intestinal epithelial cells (IECs) and intestinal intraepithelial lymphocytes (iIELs) distributed among the IECs, which constitute the first line of intestinal mucosa against infection of foreign pathogens. As an enterovirus, EV71 is transmitted by the intestinal tract; however, the mechanisms it uses to evade the immunosurveillance of the intestinal mucosal immune system are still incompletely clarified. The present study investigated how EV71 evades from recognizing and eliminating IECs, iIELs, and iNK cells. We found that EV71 infection-induced higher level of type III interferons (IFN-λ) than type Ⅰ interferons (IFN-β) in IECs and the addition of IFN-λ markedly restricted EV71 replication in IECs. These results indicate t