Aim To study the clinical value of serum pentraxin 3 (PTX3) and caveolin-1 (Cav-1) in evaluating the prognosis of thrombolytic therapy for patients with acute cerebral infarction (ACI). Methods Data of 90 ACI patients admitted to our hospital from March 2015 to September 2018 were retrospectively analyzed. All patients were treated with urokinase intravenous thrombolysis. The patients were divided into good prognosis group (n＝33) and poor prognosis group (n＝57) according to the modified Rankin scale score 90 days after treatment. Univariate analysis was used for baseline data of two groups. Non-conditional Logistic multivariate regression analysis was used to analyze the univariate factors with statistical significance in two groups. Risk factors for poor prognosis in ACI thrombolytic therapy were explored and predictive model was established. Results Serum PTX3 and Cav-1 levels in poor prognosis group were significantly higher than those in good prognosis group (t＝4.369, P＝0.000; t＝20.252, P＝0.000). Logistic regression analysis showed that interval time (OR 1.8,5%CI 0.343-5.446), blood sugar (OR 1.7,5%CI 0.917-1.724), urokinase dose (OR 1.6,5%CI 0.530-2.351), PTX3 (OR 2.9,5%CI 0.689-10.262), Cav-1 (OR 3.6,5%CI 0.644-14.879) were risk factors for poor prognosis of ACI thrombolytic therapy. ROC curve analysis showed that the cut-off value of PTX3 diagnosis was 2.38 g/L, sensitivity was 84.21%, specificity was 75.76%, area under curve (AUC) of ROC was 0.839 (95%CI 0.741-0.937); the cut-off value of Cav-1 diagnosis was 21.70 g/L, sensitivity was 75.44%, specificity was 69.70%, AUC was 0.842 (95%CI 0.744-0.940); the sensitivity, specificity and AUC of the combined detection were 91.23%, 72.73% and 0.947 (95%CI 0.896-0.999). Conclusions Interval time, blood sugar, urokinase dose, PTX3 and Cav-1 are risk factors for poor prognosis of ACI thrombolytic therapy. Detection of serum PTX3 and Cav-1 alone or in combination can be used to predict the degree of poor prognosis.