Plants have evolved numerous mechanisms that assist them in withstanding environmental stresses. Histone deacetylases (HDACs) play crucial roles in plant stress responses;however, their regulatory mechanisms remain poorly un-derstood. Here, we explored the function of HDA710/OsHDAC2, a member of the HDAC RPD3/HDA1 family, in stress tolerance in rice (Oryza sativa). We established that HDA710 lo-calizes to both the nucleus and cytoplasm and is involved in regulating the acetylation of histone H3 and H4, specifically targeting H4K5 and H4K16 under normal conditions. HDA710 tran-script accumulation levels were strongly in-duced by abiotic stresses including drought and salinity, as well as by the phytohormones jas-monic acid (JA) and abscisic acid (ABA). hda710 knockout mutant plants showed enhanced sal-inity tolerance and reduced ABA sensitivity, whereas transgenic plants overexpressing HDA710 displayed the opposite phenotypes. Moreover, ABA-and salt-stress-responsive genes, such as OsLEA3, OsABI5, OsbZIP72, and OsNHX1, were upregulated in hda710 compared with wild-type plants. These expression differences corresponded with higher levels of histone H4 acetylation in gene promoter regions in hda710 compared with the wild type under ABA and salt-stress treatment. Collectively, these results suggest that HDA710 is involved in regulating ABA-and salt-stress-responsive genes by altering H4 acetylation levels in their promoters.