Objectives To observe the expression of key proteins in the NLRP3/Caspase-1 pathway of pyroptosis in the mouse model of hepatic Echinococcus multilocularis (Em) infection and explore its correlation. Methods Twenty-five BALB/c mice were randomly divided into the control group and the infected group. The infected group was injected with 0.2 mL suspension of protoscolex (including 3 000 protoscoleces) injected under the liver capsule to establish a model of secondary infection with hepatic Em. The control group was treated without any treatments and conventional feeding was conducted. The mice were sacrificed at 1, 2, 3, and 5 months after infection. The liver was harvested and observed for gross morphology. HE staining and transmission electron microscopy were performed to observe the histopathological changes. The expressions of key proteins in the NLRP3/Caspase-1 pathway of pyroptosis and the IL-1β, a downstream factor of pyroptosis in the liver were detected by immunohistochemistry, Western blot and ELISA. Results Compared with the control group, the cystic lesions on the surface of liver tissues in the infected group mice gradually increased and protruded from the liver surface with the extension of infection time. HE staining showed various pathological changes such as inflammatory cell infiltration and fibrous hyperplasia in the liver lesions to varying degrees. After 2 months of Em infection, transmission electron microscope observation showed that the cell membrane of hepatocytes were broken and discontinuous, conforming to the "punching" phenomenon of pyroptosis. The results of ELISA showed that the concentration of IL-1β in liver homogenate of mice after 1, 2, 3 and 5 months of Em infection were significantly higher than that of the control group, and the difference was statistically significant (F=127.2, P<0.05). Immunohistochemical examination showed that the positive cell ratios of Caspase-1 and NLRP3 in liver of mice infected with Em at 1, 2, 3 and 5 months, were higher than that of the control group, and the difference were statistically significant (F=114.6, P<0.05; F=85.89, P<0.05). The Western blot results showed that the relative expression levels of Caspase-1, Xiaopi D, and NLRP3 proteins in the liver of infected mice showed a trend of first increasing (the expression of Caspase-1 and GSDMD reached their peak at 1 month of infection, while the expression of NLRP3 reached its peak at 2 months of infection) and then decreasing. There were statistically significant differences between the infection groups at different time points and the control group, as well as comparison between the infection groups at different time points there were also statistically significant differences (all P<0.05). Conclusion It is feasible to establish mouse Em infection model by “skin incision and liver puncture through abdominal muscle layer”. There is a new type of programmed cell death, pyroptosis, after Em infection in mouse liver. It may play a role in inflammation amplification through pyroptosis NLRP3/Caspase-1 pathway.