Objective To analyze the relationship between the levels of thrombo-inflammatory factors and the prognosis of intravenous thrombolysis in elderly patients with acute cerebral infarction （ACI）. Methods The 197 elderly patients with ACI admitted to our hospital from December 2020 to January 2023 were selected as study subjects. According to the prognosis of patients after intravenous thrombolysis， patients were divided into a good prognosis group （n=143） and a poor prognosis group （n=54）. The clinical data of patients in the two groups were compared. Multivariate analysis was used to identify independent risk predictors of poor prognosis in patients undergoing intravenous thrombolysis. The predictive value of thrombo-inflammatory factor levels for poor prognosis of intravenous thrombolysis in elderly patients with ACI was evaluated. A restricted cubic spline model was used to analyze the dose-response relationship between the levels of thrombo-inflammatory factors and the poor prognosis of intravenous thrombolysis in elderly patients with ACI. A nomograph model was constructed， and the effectiveness of the model was verified. Bootstrap resampling was used for external verification. Results Multivariate analysis results showed that the time from onset to receiving thrombolysis， pre-treatment National Institutes of Health Stroke Scale score，Trial of ORG 10 172 in Acute Stroke Treatment typing， monocyte chemoattractant protein-1，t-PA， sCD40L， and P-selectin levels were independent influencing factors for poor prognosis of patients undergoing intravenous thrombolysis （P<0.05）. The levels of thrombo-inflammatory factors had a certain predictive value for poor prognosis of patients undergoing intravenous thrombolysis， and the value of combined detection was higher than that of individual detection（area under the curve=820）. The dose-response relationship analysis results showed that when t-PA≤60 μg/L，the risk of poor prognosis increased with increasing t-PA level （HR 1.005，95%CI 1.003-1.007， P<0.001）；when t-PA>60 μg/L，the risk of poor prognosis almost no longer increased with increasing t-PA level （HR 1.003， 95%CI 1.001-1.006，P=0.614）. The C-index of the nomograph model was 0.814 and 0.823， and the area under the receiver operating characteristic curve was 0.861 and 0.843， indicating that the prediction model had good discrimination. The calibration curve fitted well， indicating high accuracy. The threshold probability of the clinical decision curve ranged from 0.03 to 0.95 and from 0.03 to 0.97， with a high net benefit value， indicating that the method was effective， safe， reliable， and practical. Conclusion The levels of thrombo-inflammatory factors have a certain impact on the prognosis of intravenous thrombolysis in elderly patients with ACI， and have a certain predictive value. The combined detection of various factors shows a higher predictive value.