Background and Purpose The simplified stroke-thrombolytic predictive instrument (s-Stroke-TPI) is useful for predicting the outcomes in thrombolysis-treated patients in Western populations. We aimed to validate its predictive value in Chinese patients. Methods Data from thrombolysis implementation and monitor of acute ischemic stroke in China were analyzed. Patients with acute ischemic stroke and treated with thrombolysis within 4.5 hours of symptom onset were included. The 3-month functional outcomes were assessed with the modified Rankin Scale (mRS). Model discrimination was quantified by calculating the area under receiver operating characteristic curve. s-Stroke-TPI was compared with dense artery sign, mRS score, age, glucose, onset to treatment time, and National Institutes of Health Stroke Scale or stroke prognostication using age and National Institutes of Health Stroke Scale. Results A total of 1102 patients who received thrombolysis were enrolled. The area under receiver operating characteristic curve of s-Stroke-TPI for predicting a catastrophic outcome (mRS score, 5-6), a normal/near-normal outcome (mRS score, 0-1), and independent outcome (mRS score, 0-2) at 3 months were 0.80, 0.73, and 0.75, respectively, which were significantly higher than or similar to those of dense artery sign, mRS score, age, glucose, onset to treatment time, and National Institutes of Health Stroke Scale or stroke prognostication using age and National Institutes of Health Stroke Scale. The calibration analysis of the s-Stroke-TPI showed a high correlation between the predicted and observed probabilities of the functional outcomes at 3 months. Conclusions The s-Stroke-TPI reliably predicted the 3-month functional outcomes, especially catastrophic outcomes, in Chinese stroke patients with thrombolysis. Further validation is needed to confirm outcome predictions in patients both with and without thrombolysis.