Objective To investigate the efficacy of systemic immune inflammation index (SII) at admission and National Institutes of Health Stroke Scale (NIHSS) score immediately after thrombolysis on evaluating the short-term prognosis of neurological function in patients with acute ischemic stroke (AIS) receiving intravenous thrombolysis. Methods Patients with AIS treated with intravenous thrombolysis in the Second People’s Hospital of Chengdu between March 2022 and March 2023 were retrospectively analyzed. The basic data of the patients, NIHSS score at emergency admission, NIHSS score immediately after thrombolysis, modified Rankin Scale (mRS) score 3 months after discharge, and laboratory data at admission were collected, and SII at admission was calculated. According to the mRS score 3 months after discharge, the patients were divided into the good prognosis group (mRS≤2) and the poor prognosis group (mRS>2). Multivariate logistic regression analysis was used to screen out the factors affecting the prognosis of patients, and the receiver operating characteristic curve was drawn to analyze the evaluation effect of SII at admission and NIHSS score immediately after thrombolysis on the poor prognosis of neurological function of patients in the short term. Results A total of 213 patients were enrolled, and the prognosis was poor in 88 patients. Multivariate logistic regression analysis showed that age, onset-to-needle time, uric acid at admission, SII at admission, fasting blood glucose after admission, and NIHSS score immediately after thrombolysis were independent risk factors for poor prognosis in AIS patients (P<0.05). The area under the receiver operating characteristic curve (AUC) of SII at admission for predicting poor prognosis was 0.715, the sensitivity was 55.7%, and the specificity was 84.0%. The AUC of NIHSS score immediately after thrombolysis for predicting poor prognosis of patients was 0.866, the sensitivity was 87.5%, and the specificity was 72.8%. The AUC of SII at admission combined with NIHSS score immediately after thrombolysis for predicting poor prognosis of patients was 0.875, the sensitivity was 84.1%, the specificity was 77.6%, the positive predictive value was 72.5%, and the negative predictive value was 87.4%. SII at admission was positively correlated with NIHSS score at emergency admission, NIHSS score immediately after thrombolysis, and mRS score 3 months after discharge (P<0.05). Conclusion SII at admission can predict the short-term prognosis of neurological function of patients with AIS after thrombolysis therapy, and the combination of SII at admission and NIHSS score immediately after thrombolysis can improve the prediction efficiency.