Objective: To analyze the relationship between serum homocysteine (Hcy), lipoprotein a (LP(a)) and the prognosis of intravenous thrombolysis with alteplase in patients with acute cerebral infarction. Methods: The clinical data of 70 patients with acute cerebral infarction who completed intravenous alteplase thrombolysis in our hospital from March 2022 to December 2024 were retrospectively collected. The prognosis of the patients three months after treatment was statistically analyzed, and based on this, the patients were divided into the good prognosis group and the poor prognosis group. The baseline data of the two groups and the levels of serum Hcy and Lp(a) at admission were collected and compared. To analyze the relationship between serum Hcy, Lp(a) and poor prognosis of thrombolysis. Result: Among the 70 patients, 60 had a good prognosis and were included in the good prognosis group. Ten patients had a poor prognosis and were included in the poor prognosis group. The levels of Hcy and Lp(a) at admission in the poor prognosis group were significantly higher than those in the good prognosis group (P < 0.05). The results of the Logistic regression model showed that abnormally elevated serum Hcy and Lp(a) in patients with acute cerebral infarction were risk factors for poor prognosis of alteplase thrombolytic therapy (P < 0.05). The receiver operating characteristic (ROC) curve was drawn. The area under the curve (AUC) of Hcy and Lp(a) at admission for predicting poor prognosis of intravenous thrombolysis in patients with acute cerebral infarction was both > 0.75, both of which had predictive value, and the combined predictive value was even higher. Conclusion: The serum Hcy and Lp(a) are highly expressed in patients with acute cerebral infarction, which may suggest that intravenous thrombolysis in these patients has a relatively high risk of adverse prognosis.