Abstract: Histone modification is an important epigenetic mechanism, which can be catalyzed by a variety of histone modification enzymes. In order to study the characteristics of histone modification-related genes in foxtail millet（Setaria italic L.） genome, genes were excavated in foxtail millet by comparative genomics with reference information of rice（Oryza sativa） genome. We got 80 genes related to histone modification enzymes in foxtail millet,and phy-logenetic trees were constructed according to histone acetylase/deacetylase, and methylase/demethylase,each part of which could be clustered according to their function. Identification of histone modification-related genes is an important step in elucidating the epigenetic regulation mechanism in different organisms. This study provided a preliminary theoretical basis and reference for the further study of functions and roles of these epigenetic modification-related genes in foxtail millet.