To investigate whether baseline systemic immune-inflammation index (SII) is associated with 3-month poor prognosis and early neurological outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. A total of 221 consecutive patients were enrolled in the retrospective study. The primary endpoints were poor functional outcomes or death at 3 months. Secondary endpoints were early neurological deterioration (END) or symptomatic intracerebral hemorrhage within 24 hours. Receiver operating characteristic curve analyses was performed to assess the overall discriminative ability of SII in predicting the 4 endpoints. We also performed the Spearman correlation test to evaluate the relationship between SII and stroke severity. Univariable and multivariable logistic regression analyses were performed to evaluate the associations between SII and endpoints. The cutoff values of SII were 504.99×10 9 /L for predicting a 3-month poor prognosis (sensitivity, 70.9% and specificity, 69.6%), 524.47×10 9 /L for predicting 3-month death (sensitivity, 78.9% and specificity, 59.9%) and 504.99×10 9 /L for predicting END (sensitivity, 70.7% and specificity, 62.6%), respectively. A positive association between SII and the National Institutes of Health Stroke Scale was observed ( rs = 0.306, P < 0.001). Multivariable analyses indicated that SII was independently associated with 3-month poor prognosis [odds ratio (OR) = 5.384; 95% CI: 2.844-10.193; P < 0.001], 3-month death (OR = 2.592, 95% CI: 1.046-6.421, P = 0.040) and END (OR = 3.202, 95% CI: 1.796-5.707, P < 0.001). Increased baseline SII was associated with END and 3-month poor outcomes, and may act as a potential prognostic predictor for acute ischemic stroke patients treated with intravenous thrombolysis.