Objective To investigate the relationship between serum homocysteine（ Hcy） and seizure control as well as cognitive impairment in patients with epilepsy（ MCI）. Methods A total of 128 cases of epilepsy patients were enrolled and assessed for cognitive function with Mini-Mental State Evaluation Scale （MMSE）. According to the existence of MCI， all the subjects were assigned into MCI group（ n=46）， and non-MCI group（ n=82）. The levels of folic acid， Hcy， vitamin B12 in serum of patients were determined by chemiluminescence immunoassay. The correlation between serum Hcy and the score of MMSE were analyzed by Pearson correlation analysis. High homocysteine（ HHcy） epilepsy patients were treated with folic acid and vitamin B. The serum Hcy level and the seizure frequency were analyzed before treatment， 3 months and 6 months after treatment. Results The serum Hcy level of HHcy patients at 3 months and 6 months after treatment decreased significantly， so as the seizure frequency（ P ＜ 0.01）. Compared with non-MCI group， serum folic level and vitamin B12 decreased significantly（P＜0.05）， while the Hcy level increased（ P＜0.01）. When serum Hcy was less than 15.00 μmol/L， there was no significant correlation with MMSE（ r=-0.18， P＞ 0.05）. When serum Hcy level was between 15.0～20.0 μmol/L and over 20.0 μmol/L，there was a negative correlation between MMSE and serum Hcy level（ r=-0.39，-0.56；P＜0.05）. Conclusions Giving vitamin B12 intervention to HHcy epilepsy patients can reduce serum Hcy levels and the frequency of seizures. Whether the level of Hcy in epileptic patients can be used as a biological predictor of MCI in epileptic patients still needs to be classified accurately.