Objective To investigate the association of Per2C111G gene polymorphisms with sleep-related epilepsy in a Han population in Hunan Province. Methods Three hundred Han epileptic patients and 100 healthy controls from Hunan Province were enrolled in the study. According to sleep/wake patterns of seizures, the epileptic patients were divided into 3 groups: sleep epilepsy, wakefulness epilepsy and aperiodic epilepsy. Per2C111G gene polymorphisms were investigated by polymerase chain reaction (PCR) and gene sequencing. Results The frequency of Per2 site C111G genotypes in the Han population in Hunan was 87.0% (CC), 13.0% (CG) and 0.0% (GG). C and G allele gene frequencies were 93.5% and 6.5% respectively. There were no significant differences in both the genotype frequency and allele frequency in Per2C111G between epileptic patients and controls. There were also no significant differences among 3 subgroups of epileptic patients (P>0.05). Conclusions Per2C111G gene polymorphisms may not be associated with sleep-related epilepsy in the Han population of Hunan Province.