High mobility group box-1 (HMGB1) is a non-histone, DNA-binding nuclear protein belonging to the family of damage-associated molecular patterns (DAMPs). HMGB1 has been reported to play an important role during epileptogenesis although the mechanisms of its actions are still not clear. Many hypotheses have been suggested especially about the relationship between HMGB1 and inflammation responses and blood-brain barrier disruption during epileptogenesis. In this review, we will mainly discuss the role of HMGB1 in epileptogenesis.