Soybean is an important crop worldwide, but its production is severely affected by salt stress. Understanding the regulatory mechanism of salt response is crucial for improving the salt tolerance of soybean. Here, we reveal a role for nuclear factor Y subunit GmNFYA in salt tolerance of soybean likely through regulation of histone acetylation. GmNFYA is induced by salt stress. Overexpression of GmNFYA significantly enhances salt tolerance in stable transgenic soybean plants by inducing salt-responsive genes. Analysis in soybean plants with transgenic hairy roots also supports the conclusion. GmNFYA interacts with GmFVE, which functions with putative histone deacetylase GmHDA13 in a complex for transcriptional repression possibly by reducing H3K9 acetylation at target loci. Under salt stress, GmNFYA likely accumulates and competes with GmHDA13 for interaction with GmFVE, leading to derepression and maintenance of histone acetylation for activation of salt-responsive genes, and finally conferring salt tolerance in soybean plants. In addition, a haplotype I GmNFYA promoter is identified with highest self-activated promoter activity and may be selected during future breeding for salt tolerant cultivars. Our study uncovers the epigenetic regulatory mechanism of GmNFYA in salt-stress response and all the factors/elements identified may be potential targets for genetic manipulation of salt tolerance in soybean and other crops.