Objective To investigate the predictors of systemic inflammatory response syndrome (SIRS) in patients with acute ischemic stroke. Methods The patients with acute ischemic stroke admitted to hospital from January 2010 to April 2014 were enroled. The demographics, vascular risk factors, baseline clinical data, and laboratory tests in both groups were colected. Flow cytometry was used to analyze the peripheral blood T helper cel (Th) subgroup. Double antibody sandwich enzyme-linked immunosorbent assay was used to detect the levels of peripheral blood interferon-γ (IFN-γ) and interleukin-4 (IL-4). Results A total of 143 patients with acute ischemic stroke were enroled, including 56 in a SIRS group and 87 in a non-SIRS group. Univariate analysis showed that there were significant differences in the history of hypertension, history of stroke, baseline systolic blood pressure, low-density lipoprotein cholesterol level, National Institutes of Health Stroke Scale (NIHSS) score, percentage of Th1 cels, and IFN-γ concentration in patients of both groups (al P < 0. 05). Multivariate logistic regression analysis showed that the NIHSS score ≥6 (odds ratio [ OR] 2. 40, 95% confidence interval [ CI] 1. 24 - 5. 15, P = 0. 008), decreased percentage of Th1 cels (OR 2. 81, 95% CI 1. 51 - 6. 83, P = 0. 013), and decreased IFN-γ concentration (OR 4. 63, 95% CI 1. 01 - 9. 72, P = 0. 004) were the independent predictive factors for occurring SIRS in patients with acute ischemic stroke. Conclusions Severe neurological deficit, decreased percentage of Th1 cels or decreased IFN-γ level may increase the risk of acute ischemic stroke patients with SIRS.