[Background] Enterovirus 71 (EV71) is likely to cause severe hand, foot, and mouth disease (HFMD) that is sometimes associated with severe central nervous system complications, resulting in poor prognosis and even death of children. [Objective] To reveal the possible miRNA mechanism of EV71 increasing autophagy in human neuroblastoma cells, which might be related to EV71 induced neurological damage. [Methods] Western blot and qRT-PCR were used to demonstrate autophagy in EV71 infected SH-SY5Y cells. The differentially expressed miRNAs in SH-SY5Y cells with/without EV71 infection were detected by qPCR-Array. The functions of those miRNAs were analyzed by bioinformatics method. Then miRNA mimics was used to identify miRNAs associated with EV71-induced neuronal autophagy. [Results] EV71 could increase autophagy in SH-SY5Y cells and decrease the expression of miRNA29b in cells. Moreover, transfection of miRNA29b mimics in cells could not only reverse the down-regulated expression of miRNA29b induced by EV71, but also decrease the cellular autophagy induced by EV71 and the level of viral replication. [Conclusion] The results indicated that EV71 could induce autophagy in SH-SY5Y cells by down-regulating the expression of miRNA29b. Moreover, miRNA29b might be related to virus replication. Therefore, this study not only helps elucidate the specific molecular mechanism of neurological damage caused by EV71, but also lays a theoretical foundation for miRNA29b to become a new potential drug target for the treatment of EV71 infection.