Simple febrile convulsion (SFC) is one common disease in clinic. As is well-known, SFC is mainly caused by fever from extracranial infectious disease. Classically, Because of unclear pathogenesis and no reliable biomarkers of SFC, pediatricians usually use fever degree, type of convulsion, duration of symptom, and convulsion frequency in 24 hours to make diagnosis. In our study, in order to find whether there are some changes in serum after episode of convulsion, we utilized proteomic approaches to quantify the proteome of serum from patients who were diagnosed with SFC compared to healthy control children. We found about seven hundred proteins involed in different biological pathways including coagulation system related proteins in serum, and 86 of them had statistical difference between SFC group and control group. The 35 altered proteins had a higher expression levels with the others a lower expression levels in SFC group compared to control group. The fibrinogen related proteins involved in coagulation system pathway are highly remarkable declined in SFC group, which means that those proteins may distribute to brain during the course of disease to induce inflammatory response as considered to be the reason of convulsion. These results highlight a potential mechanism about how convulsion happen in SFC, and fibrinogen related proteins may be the potential biomarkers used in the diagnosis of SFC in future.