Objective To study serum levels of neuron specific enolase (NSE) and insulin-like growth factor-1 (IGF-1) in patients with epilepsy and their significance. Methods Sixty-three patients with idiopathic epilepsy were enrolled in this study. Serum NSE and IGF-1 levels were determined using ECLIA and ELISA within 3 days after seizure attacks. Thirty-seven healthy volunteers served as control group matched with age and sex to the epilepsy group. Results Serum NSE and IGF-1 levels increased significantly in the epilepsy group compared with the control group (P<0.05). The area under the ROC curve of serum NSE and IGF-1 was 0.767 and 0.663 respectively. Serum NSE level was positively correlated with serum IGF-1 level (r=0.379, P<0.01) in the epilepsy group. Conclusions Serum NSE and IGF-1 levels increase within 3 days after seizure attacks, suggesting that they might be used as early biochemical indicators of seizure-induced brain damage and neuroprotection starting. A positive correlation between serum NSE and IGF-1 levels indicates that they might participate in the process of seizures together.