Abstract: Objective　To investigate the effect of interferon regulatory factor-1 (IRF-1) on the pyroptosis of liver ischemia reperfusion injury (LIRI) in mice. Methods　(1) Twenty four C57BL / 6 normal male mice were randomly divided into sham operation group (Sham) and ischemia-reperfusion (IR) 2 h, 6 h and 12 h groups, 6 mice in each group. The Sham group was not treated with IR, while in the other three groups, the LIRI model was established by clamping the middle lobe and left lobe of liver with vascular clamp for 60 min and reperfusion for 2,6 and 12 h respectively. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and interleukin (IL)-1β were detected by enzyme-linked immunosorbent assay (ELISA). The pathological changes of liver were observed by HE staining. The expression of IRF-1 was detected by immunohistochemical staining. The apoptosis and pyroptosis of liver cells were detected by TUNEL. The protein levels of IRF-1, Caspase-1 and gasdermin D (GSDMD) were detected by Western blot assay. The morphological changes of hepatocytes were detected by transmission electron microscope. (2) The AML12 cells in the normal liver of mice were over expressed and silenced of IRF-1, and then subjected to the simulated IR treatment. The AML12 cells were divided into over expression IRF-1+IR group, empty vector + IR group, IRF-1 siRNA + IR group and control group (NC+IR group). Western blot assay was used to detect the levels of IRF-1, Caspase-1, Cleaved-Caspase-1 and GSDMD proteins in the four groups. Transmission electron microscopy was used to detect cell morphological changes. Apoptosis and pyroptosis of cells were detected by flow cytometry. The release of lactate dehydrogenase (LDH) in cell supernatant was detected by microplate reader. Results　(1) The results in vivo showed that compared with the Sham group, the serum levels of ALT, AST and IL-1β were significantly increased in the IR 6 h and IR 12 h groups (P < 0.05), and the expression levels of IRF-1, Caspase-1 and GSDMD proteins were increased (P < 0.05). At the same time, liver cells appeared swelling, disordered arrangement, vacuoles, pathcy necrosis and erythrocyte siltation, accompanied by nuclear membrane damage and mitochondrial swelling. (2) After the over expression of IRF-1 in AML12 cells in vitro, the expressions of Cleaved-Caspase-1 and GSDMD increased, while the expressions of Caspase-1 and GSDMD decreased after the down-regulation of IRF-1 expression (P＜0.05). After silencing IRF-1 expression, the damage of cytoplasmic membrane and nuclear membrane was reduced in IRF-1 siRNA + IR group than that of NC + IR group, the pyroptosis rate was decreased, and the LDH release was reduced by about 20%. Conclusion　IRF-1 can induce LIRI in mice by regulating the expressions of Caspase-1 and GSDMD and the release of IL-1β.