Abstract: Objective To discuss the expression of NLR family CARD domain-containing protein 4 (NLRC4) and its relationship with acute cerebral infarction (ACI). Methods A total of 39 ACI patients who were admitted in the Affiliated Huaihai Hospital of Xuzhou Medical University from May 2019 to August 2020 were selected and set as a study group. Meanwhile, 40 patients who underwent physical examination in our hospital were selected as a control group. The expression of NLRC4, interleukin (IL)-1β and IL-18 in the peripheral blood of patients and rats were detected by ELISA. Then, an ACI rat model was established by blocking the blood flow of middle cerebral artery for 24 h. Immunofluorescence staining and Western blot were used to detect the expression of the NLRC4 in ischemic and sham operated brain tissue. Results Compared with the control group, the study group showed no statistical difference in age, sex, body mass index and diabetic and smoking history (P＞0.05), with an increased proportion of hypertension (P＜0.05). For blood biochemical tests, compared with the control group, the level of C-reactive protein in ACI patients significantly increased, but high-density lipoprotein levels were reduced (P＜0.05). ELISA results showed that the levels of NLRC4 and IL-1β in the peripheral blood of ACI patients were significantly up-regulated (P＜0.05). Immunofluorescence staining confirmed that the expression of NLRC4 in ischemic-injured neurons increased. According to ELISA results, the levels of NLRC4, IL-1β and IL-18 in the peripheral blood of ACI rats were remarkably higher than those in the control groups (P＜0.05). Conclusions NLRC4 and its medicated inflammasome signals are remarkably up-regulated in ACI tissues, which suggest its potential role as a therapeutic target for stroke.