Objective To investigate the effects of Echinococcus multilocularis infection on the proportion of type 1 innate lymphoid cells (ILC1) and the expression levels of related factors in the spleen of mice. Methods C57BL/6J mice were randomly divided into the control group and the infection group. The infection group mice were injected with 3 000 E. multilocularis protoscoleces via the portal vein, while the control group mice were injected with the same volume of normal saline. After 24 weeks, spleen tissue sections were prepared from the infection group and the control group mice, and hematoxylin-eosin (HE) staining was used to observe the pathological changes in the spleen. Splenic lymphocytes were isolated from the mice, and flow cytometry was used to detect the proportion of ILC1 cell subsets, the expression of immune checkpoint molecules, and the levels of secreted cytokines in the spleen. Results HE staining showed that the boundary between the red pulp and the marginal zone of the white pulp was blurred in the spleen of mice infected with E. multilocularis, and hemosiderin deposition occurred in the white pulp area. Flow cytometry results indicated that the percentage of splenic natural killer (NK) cells among total splenic lymphocytes in the control group was (2.52 ± 0.44)%, which was higher than that in the infection group (1.25 ± 0.28)% (t = 6.42，P < 0.01). The percentage of splenic ILC1 among splenic NK cells in the control group was (20.07 ± 2.70)%, which was lower than that in the infection group (31.49 ± 3.28)% (t = 7.10, P < 0.01). The percentage of splenic conventional NK (cNK) cells among splenic NK cells in the infection group was (68.89 ± 3.28)%, which was lower than that in the control group (80.14 ± 3.49)% (t = 6.22, P < 0.01). The percentage of CD27^-CD11b⁺ cells among splenic ILC1 in the infection group was (21.37 ± 7.48)%, which was lower than that in the control group (43.49 ± 8.05)% (t = 5.33, P < 0.01); the percentages of CD27⁺CD11b^- and CD27⁺CD11b⁺ cells were (39.64 ± 8.80)% and (6.77 ± 1.51)%, respectively, which were higher than those in the control group (24.51 ± 8.35)% and (4.12 ± 1.71)% (t = 3.30, 3.06; both P < 0.01). The percentages of splenic ILC1 secreting programmed death receptor 1 (PD-1) and glucocorticoid-induced tumor necrosis factor receptor (GITR) in the infection group were (5.04 ± 1.54)% and (16.14 ± 4.53)%, respectively, which were higher than those in the control group (2.57 ± 1.52)% and (10.81 ± 4.03)% (t = 3.02, 2.33; both P < 0.05). The percentages of splenic ILC1 secreting granzyme B (Gr-B) and interferon-γ (IFN-γ) in the infection group were (6.16 ± 1.23)% and (16.13 ± 6.64)%, respectively, which were lower than those in the control group (9.42 ± 2.16)% and (30.68 ± 6.81)% (t = 2.94, 3.42; P < 0.05, 0.01). The percentage of splenic ILC1 secreting tumor necrosis factor-α (TNF-α) in the infection group was (22.26 ± 6.69)%, which was higher than that in the control group (10.80 ± 3.92)% (t = 3.31, P < 0.05). Conclusion In the late stage of E. multilocularis infection, the proportion of ILC1 cells and immature ILC1 cells were increased in mouse spleen. The co-inhibitory immune checkpoint molecule PD-1 was highly expressed, and the ability of these cells to secrete cytokines Gr-B and IFN-γ decreased. This suggested that ILC1 cell function suppressed might promote the chronic parasitism of E. multilocularis.