Various studies suggested that brain-derived neurotrophic factor (BDNF) gene polymorphisms contributed to the development of many neurological disorders. However, whether BDNF Val66Met polymorphism is associated with epilepsy remains controversial. In our study, we tried to investigate the effects of this functional polymorphism on the occurrence of temporal lobe epilepsy (TLE) and its clinical phenotypes. Case-control studies were employed to study the association between BDNF Val66Met polymorphism and TLE, as well as its clinical phenotypes, and magnetic resonance imaging examinations and voxel-based morphometry analyses were carried out for further study. Our results showed that the frequency of Met allele was found to be lower in the TLE patients compared with the control subjects (43.9% vs. 48.6%, P = 0.012, OR = 1.21, 95% CI= 1.04-1.41), and the frequency of Met66 allele carriers in the TLE with hippocampal sclerosis was significantly lower than those non-carriers (20.5% vs. 29.1%, P = 0.040). However, we failed to find the difference between different genotypes and hippocampal asymmetry. Our findings suggested that BDNF Val66Met polymorphism might be correlated with epileptogenesis, and Met66 allele might play a protective role against the occurrence of TLE.