Echinococcus multiloculasis is a zoonotic parasitic disease caused by Echinococcus multilocularis, which can cause liver injury, but the mechanism of liver injury is still unclear. Here, Echinococcus multilocularis was injected via the hepatic portal vein to establish a mouse model of infection, and high-throughput RNA sequencing was performed for detecting the expression of miRNAs in the liver of mice infected with 2000 Echinococcus multilocularis after 3 months infection, in order to understand the potential molecular mechanism of liver injury caused by Echinococcus multilocularis infection. Overall, 71 differentially expressed miRNAs were found in liver in comparison with control and a total of 36 mouse miRNAs with |FC|>0.585 were screened out, respectively. In addition, Targetscan (V5.0) and miRanda (v3.3a) software were used to predict differential miRNAs target genes and functional enrichment of target genes. Functional annotation showed that “cytokine-cytokine interaction”, “ positive regulation of cytokine production”, “ inflammatory respose”, “ leukocute activation” were enriched in the liver of Echinococcus multilocularis-infected mice. Moreover, the pathways “human cytomegalovirus infection”, “cysteine and methonine metabolism”, “Notch signaling pathway” and “ferroptosis” were involved in liver disease. Furthermore, 4 miRNAs (mmu-miR-30e-3p, mmu-miR-203-3p, mmu-miR-125b-5p and mmu-miR-30c-2-3p) related to liver injury were screened and verified. This study revealed that the expression profiling of miRNAs in the livers was changed after Echinococcus multilocularis infection, and improved our understanding of the transcriptomic landscape of hepatic echinococcosis in mice.