Duck Tembusu virus (DTMUV) infection triggers the innate immunity signaling pathways in the cell. Both MDA5 and TLR3 can recognize DTMUV and elicit signaling cascades through adaptor proteins MAVS and TRIF, respectively, leading to the induction of IFN-I production. The JAK-STAT signaling pathways mediated by IFN-I induce the abundant expression of various ISGs, including Mx, OASL, IFITMs, Viperin etc., and they are capable of inhibiting DTMUV replication. However, the specific role of other PRRs such as RIG-I, TLR7, DDX/DHX, and HMGBs is unclear, it needs further study. To date, DTMUV has evolved several strategies to escape from host immune responses. The protein NS1 of DTMUV can bind MAVS to impair the IFN-I expression level. NS2A and NS2B3 target the transcription molecule STING to inhibit the IFN-I, resulting in the immune evasion. Additionally, DTMUV may downregulate the expression of TLR3 by microRNA-148a-5p.