Objective To investigate the relationship between systemic inflammation response index (SIRI) and early neurological deterioration (END) and 3-month prognosis in patients with acute ischemic stroke. Methods Patients with acute ischemic stroke treated at West China Hospital of Sichuan University and Deyang People’s Hospital between April 2020 and October 2020 were collected. Clinical data were collected using a unified case form and outcomes were followed up for 3 months. According to the poor prognosis, the patients were divided into END group and non-END group. The multivariate logistic regression analysis was used to explore the relationship of SIRI, END and 3-month prognosis. We drew receiver operating characteristic curve to evaluate the value of related factors in predicting the occurrence of END and poor prognosis after 3 months. Results A total of 242 patients were included, of which 47 (19.42%) were in the END group. There were statistically significant differences between the two groups in National Institutes of Health stroke Scale (NIHSS) score on admission, hypertension, creatinine, urea nitrogen, neutrophils count, lymphocyte count, neutrophil count/lymphocyte count ratio (NLR), lymphocyte count/monocyte count ratio, platelet count/lymphocyte count ratio, complications (besides cerebral edema) and SIRI (P<0.05). Logistic regression analysis showed that NIHSS score on admission, hypertension, SIRI and NLR were independent risk factors for END (P<0.05). SIRI had better predictive value for the occurrence of END than NLR (P<0.05). Compared with the non-END group, the patients in the END group had worse prognosis at 3-month [44.7%(21/47) vs. 17.4% (34/195), P<0.05]. NIHSS score on admission had predictive value for clinical prognosis of acute ischemic stroke patients at 3-month. Conclusion SIRI is an independent risk factor for END in patients with acute ischemic stroke, and there is no independent correlation with the 3-month prognosis.