Hand, foot, and mouth disease (HFMD) is a serious threat to the health of infants, and it can be caused by enterovirus 71 (EV71). The clinical symptoms are mostly self-limiting, but some infections develop into aseptic meningitis with poor prognosis and even death. In this study, urolithin A (UroA), an intestinal metabolite of ellagic acid, significantly inhibited the replication of EV71 in cells. Further evaluation showed that UroA was better than ribavirin in terms of its 50% cytopathic concentration (CC50), 50% inhibitory concentration (IC50), and selectivity index. Moreover, UroA inhibited the proliferation of EV71 by promoting autophagy and apoptosis of infected cells. Therefore, UroA is a candidate drug for the treatment of EV71 infection.