Frontal lobe epilepsy (FLE) is one common type of epileptic in clinic. Some FLE patients could be cured by surgery treatment. This study is designed to find out if there are some differential protein expressions in serum between pre and post operation of the seizure-free FLE patients. We have utilized proteomic approaches to quantify the proteome of serum from 5 surgery patients who were diagnosed with FLE. The self-control method was used in the study, and serum samples from two time periods, including pre-operation and one year after the surgery were selected. We have found about six hundred proteins in serum, and 14 of them had statistical difference between pre and post operation. 13 proteins including 3 apolipoprotein subtypes (APOA2, APOC1, and APOC2) had a higher expression levels with the other one a lower expression level in the pre-operation group compared to the post-operation group. This method may highlight a potential way to explore refractory epilepsy biomarkers, and some apolipoprotein subtypes may be the potential biomarkers used in the diagnosis of FLE in the future.