ObjectiveTo explore the role of miRNA in liver damage caused by Echinococcus multilocularis infection.MethodsSix female C57BL mice were randomly divided into two groups, the control group and the infection group. Mice in the control group were injected with 100 μL PBS through the hepatic portal vein, and mice in the infection group were infected with E. multilocularis via the hepatic portal vein to establish a mouse model of infection. Small RNA sequencing was performed for detecting the expression of miRNAs in the liver of mice infected with 2000 E. multilocularis after 3 months of infection, screen out miRNAs related to liver damage, and verify by RT‐PCR.ResultsSeventy‐one differentially expressed miRNAs were found in the 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 response,” and “leukocyte activation” were enriched in the liver of E. multilocularis‐infected mice. Moreover, the pathways “human cytomegalovirus infection,” “cysteine and methionine metabolism,” “Notch signaling pathway,” and “ferroptosis” were involved in liver disease. Furthermore, four 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.ConclusionThis study revealed that the expression profiling of miRNAs in the livers was changed after E. multilocularis infection, and improved our understanding of the transcriptomic landscape of hepatic echinococcosis in mice.