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Background: Symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis is closely related to the poor outcome of stroke., Aims: To determine the serum biomarkers associated with sICH based on the INTRECIS study., Methods: Enrolled patients with sICH and without any ICH were matched by propensity score matching with the ratio of 1:1. Preset 49 biomarkers were measured by protein microarray analysis. Gene Ontology and Pathway Enrichment Analysis and protein-protein interaction network (PPI) were analyzed in the identified biomarkers., Results: Of the consecutive 358 patients, eight patients occurred with sICH, which was assigned as an sICH group, while eight matched patients without any ICH were assigned as a Non-sICH group. A total of nine biomarkers were found significantly different between groups, among which the levels of interferon (IFN)-γ and interleukin (IL)-4 were higher, while the levels of C-reactive protein (CRP), glial cell line-derived neurotrophic factor (GDNF), insulin-like growth factor-binding protein (IGFBP)-6, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, matrix metalloprotein (MMP)-2, plasminogen activator inhibitor (PAI)-1, and platelet-derived growth factor (PDGF)-AA were lower in the sICH group compared with those in the Non-sICH group., Conclusions: Our finding indicated that baseline serum CRP, GDNF, IFN-γ, IGFBP-6, IL-4, LYVE-1, MMP-2, PAI-1, and PDGF-AA levels were associated with post-thrombolytic sICH in stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cui, Zhao, Chen, Sheng, Wang, Meng and Chen.)