The excess soluble salts in soil are harmful to most plants growth and development. Evidence is emerging that plant cell wall is involved in sensing of and response to salt stress, but the underlying mechanisms are not well understood. We reveal that histone acetyltransferase GENERALCONTROL NON-REPRESSED PROTEIN 5 (GCN5) is required for cell wall integrity maintenance and salt stress tolerance. GCN5 mRNA levels are increased in response to salt stress. The gcn5 mutants exhibited severe growth inhibition and cell wall integrity defects under salt stress condition. Combining RNA-Seq and ChIP assays, we identified CHITINASE-LIKE gene (CTL1), POLYGALACTURONASE INVOLVED INEXPANSION-3 (PGX3) and MYB DOMAIN PROTEIN-54 (MYB54) as direct targets of GCN5. GCN5-mediatedH3K9 and H3K14 acetylation is associated with CTL1, PGX3 and MYB54 activation under salt stress. Moreover, a constitutive expression of CTL1 in gcn5 mutant restores the salt tolerance and cell wall integrity. In addition, the expression of wheat TaGCN5 gene in Arabidopsis gcn5 mutant plants complemented the salt tolerance and cell wall integrity phenotypes, suggesting that GCN5-mediated salt tolerance is conserved between Arabidopsis and wheat. Taken together, our data indicate that GCN5plays a key role in the preservation of salt tolerance via versatile regulation in plants.