BACKGROUND: Modification of histone acetylation is a ubiquitous and reversible process in eukaryotes and prokaryotes and plays crucial roles in the regulation of gene expression during plant development and stress responses. Histone acetylation is co-regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC). HAT plays an essential regulatory role in various growth and development processes by modifying the chromatin structure through interactions with other histone modifications and transcription factors in eukaryotic cells, affecting the transcription of genes. Comprehensive analyses of HAT genes have been performed in Arabidopsis thaliana and Oryza sativa. However, little information is available on the HAT genes in foxtail millet (Setaria italica [L.] P. Beauv). RESULTS: In this study, 24 HAT genes (SiHATs) were identified and divided into four groups with conserved gene structures via motif composition analysis. Phylogenetic analysis of the genes was performed to predict functional similarities between Arabidopsis thaliana, Oryza sativa, and foxtail millet; 19 and 2 orthologous gene pairs were individually identified. Moreover, all identified HAT gene pairs likely underwent purified selection based on their non-synonymous/synonymous nucleotide substitutions. Using published transcriptome data, we found that SiHAT genes were preferentially expressed in some tissues and organs. Stress responses were also examined, and data showed that SiHAT gene transcription was influenced by drought, salt, low nitrogen, and low phosphorus stress, and that the expression of four SiHATs was altered as a result of infection by Sclerospora graminicola. CONCLUSIONS: Results indicated that histone acetylation may play an important role in plant growth and development and stress adaptations. These findings suggest that SiHATs play specific roles in the response to abiotic stress and viral infection. This study lays a foundation for further analysis of the biological functions of SiHATs in foxtail millet.