To investigate the serum biomarkers in acute ischemic stroke (AIS) patients that may be of potential diagnostic significance. Methods: Blood serum from 73 acute ischemic stroke patients and 53 health controls was collected. Proteins were isolated from serum samples then analyzed using the proteomics approach of isobaric tagging for relative and absolute quantitation (iTRAQ) to compare the differentially expressed proteins between the two groups. Bioinformatics was used for conformation and analysis, and the western blot was employed for further validation. The receiver operating characteristic (ROC) curve was created and the area under the curve (AUC) was calculated, and the relationship between differential protein expression and the occurrence of acute ischemic stroke was assessed. Results: Expression of pro-platelet basic protein (PPBP) showed a 1.47-fold increase in the AIS group (P<0.01) compared to that in the control group. Western blot revealed that PPBP expression in the AIS group was 1.62 times higher than that in the control group (P<0.01). With PPBP expression quantity as the test variable and patient or control as the status variable, we created the ROC curve which yielded AUC=0.7539, 95% CI=0.638~0.870 (P<0.01). Conclusion: The serum level of PPBP in AIS patients was significantly increased. PPBP may be a potential biomarker for the early diagnosis of AIS.