【】 Objective To observe the effect of EV71-induced skeletal muscle injury and to explore the mechanism of Caspase-1/IL-1β signaling pathway in EV71-induced skeletal muscle injury. Methods The 1-day-old BALB/c suckling mice were randomly divided into three groups: normal group (60 pigs), EV71 model group (60 pigs), and cysteinyl aspartate specific proteinase (Caspase)-1 inhibitor (VX765) group (15 pigs). The normal group and the model group were randomly divided into 4 subgroups: 5, 7, 10 and 14d, with 15 animals in each subgroup. 25*103 μl/kg of EV71 virus solution was intraperitoneally injected into one-day-old BALB/c suckling mice for 3 consecutive days. Caspase-1 inhibitor VX765 (20 mg/kg) was injected intraperitoneally 6 hours after virus inoculation, and inoculated daily until the sample was collected. After successful modeling, the body weight and disease scores of BALB/c suckling mice in each group were recorded, hematoxylin-eosin staining (HE) was used to observe the pathological damage of skeletal muscle, and Western blotting and immunofluorescence (IF) were used to detect EV71 VP-1 (EV71 virus-specific capsid protein), pro-caspase-1, Expression of cleaved-caspase-1, IL-1β, a-SMA, and Collegen I proteins. Results Compared with the normal group at the same time point, the EV71 model group had a reduced body weight and increased disease scores. HE staining of skeletal muscle tissue in suckling mice in the EV71 model group showed a large infiltration of inflammatory cells, muscle fascicle rupture and lysis, and a decrease in the cross-sectional area of muscle tissue. Western blot results showed that the levels of EV71 VP-1, IL-1β, a-SMA and Collegen I in the homogenate of skeletal muscle tissue at 5d, 7d and 10d in the EV71 model group were significantly increased (P<0.05). Compared with the EV71 model group, the body weight and clinical disease score of the VX765 group were increased (P<0.05), and the results of Western blot and immunofluorescence showed that Caspase-1 inhibitor could significantly reduce the expression of EV71 VP-1 protein in the homogenate of skeletal muscle tissue of the EV71 model group, and down-regulate pro-caspase-1, cleaved-caspase-1, IL-1β and Collegen I protein level (P<0.05), inhibition of caspase-1 attenuated the effect of EV71 virus on skeletal muscle injury in BALB/c suckling mice. Conclusion EV71 may induce skeletal muscle injury by activating the Caspase-1/IL-1 signaling pathway.