Salinity is a significant environmental challenge that threatens global food security. This study investigates the role of the miR396b/GRF6 module in enhancing salt tolerance in rice. The authors found that the miR396b/GRF6 module significantly improved salt tolerance in rice, with transgenic lines showing a 48.0% and 74.4% increase in survival rates compared to the wild type. The module also reduced H2O2 accumulation and increased the activities of ROS-scavenging enzymes (CAT, SOD, and POD). The study identified ZNF9, a negative regulator of rice salt tolerance, which directly binds to the promoter of miR396b to modulate its expression. Transcriptome and ChIP-seq analysis revealed that MYB3R serves as a downstream target of miR396b/GRF6 and its overexpression significantly enhanced salt tolerance. These findings provide valuable insights into the molecular mechanisms underlying the response of the miR396b/GRF6 network to salt stress in rice, offering potential genetic resources for breeding high-yield, salt-tolerant rice varieties.Salinity is a significant environmental challenge that threatens global food security. This study investigates the role of the miR396b/GRF6 module in enhancing salt tolerance in rice. The authors found that the miR396b/GRF6 module significantly improved salt tolerance in rice, with transgenic lines showing a 48.0% and 74.4% increase in survival rates compared to the wild type. The module also reduced H2O2 accumulation and increased the activities of ROS-scavenging enzymes (CAT, SOD, and POD). The study identified ZNF9, a negative regulator of rice salt tolerance, which directly binds to the promoter of miR396b to modulate its expression. Transcriptome and ChIP-seq analysis revealed that MYB3R serves as a downstream target of miR396b/GRF6 and its overexpression significantly enhanced salt tolerance. These findings provide valuable insights into the molecular mechanisms underlying the response of the miR396b/GRF6 network to salt stress in rice, offering potential genetic resources for breeding high-yield, salt-tolerant rice varieties.