Salt stress significantly inhibits crop growth and development, and mitigating this can enhance salt tolerance in various crops. Previous studies have shown that regulating saccharide biosynthesis is a key aspect of plant salt tolerance
however, the underlying molecular mechanisms remain largely unexplored. In this study, we demonstrate that overexpression of a salt-inducible galactinol synthase gene, ZmGolS1, alleviates salt-induced growth inhibition, likely by promoting raffinose synthesis. Additionally, we show that natural variation in ZmGolS1 transcript levels contributes to the diversity of raffinose content and salt tolerance in maize. We further reveal that ZmRR18, a type-B response regulator transcription factor, binds to the AATC element in the promoter of ZmGolS1, with this binding increases the transcript levels of ZmGolS1 under salt conditions. Moreover, a single nucleotide polymorphism (termed SNP-302T) within the ZmGolS1 promoter significantly reduces its binding affinity for ZmRR18, resulting in decreased ZmGolS1 expression and diminished raffinose content, ultimately leading to a salt-hypersensitive phenotype. Collectively, our findings reveal the molecular mechanisms by which the ZmRR18-ZmGolS1 module enhances raffinose biosynthesis, thereby promoting maize growth under salt conditions. This research provides important insights into salt tolerance mechanisms associated with saccharide biosynthesis and identifies valuable genetic loci for breeding salt-tolerant maize varieties.