Optimal Balance between high yield and stress tolerance is the goal of breeding, which is related to the strategy in choice of both ways. The questions such as which negative regulators of stress tolerance affect yield and how they function are important issues for breeding. Over the past century, owing to the breeding of high-yield varieties, the maize yield has been tremendously increased, but this is accompanied with the increased sensitivity to environmental stresses, and the genetic mechanisms underlying this phenomenon remains elusive. This restricts the breeding of maize cultivars with both high yield and stress tolerance. Both yield traits and stress tolerance are complex quantitative traits, determined by the expression and regulation of a large number of genes. Small RNAs (sRNAs) are important gene expression regulators, and they are generated in large quantities from the maize genome. But the mechanisms underlying their regulation on crop stress responses and yield traits remain largely elusive. Recently, the group of Prof. Mingqiu Dai, collaborated with the groups of Prof. Lin Li and Prof. Feng Li at Huazhong Agricultural University, identified about ten-thousands of drought-responsive sRNAs and eQTLs associated with the expression of these sRNAs, by analyzing the sRNAome and transcriptome of a maize panel consisting 338 natural inbred lines grown under different environment conditions. They cloned an eQTL hotspot named DRESH8, which is a Transposable Element-mediated Inverted Repeat (TE-IR) in a length of about 21.4 kb. Genetic and molecular evidence showed that DRESH8-derived siRNAs directly inhibit the expression of the drought-resistant genes via a post-transcriptional silencing mechanism, and indirectly inhibit the expression of negative regulators of yield-related traits, thus negatively regulating drought response and positively regulate yield-related traits. Further analysis demonstrated that DRESH8 was selected during maize domestication and improvement. Their findings suggest that DRESH8 is a key genetic locus that balances maize yield and drought tolerance, and that IR-mediated balance between maize yield and drought resistance may be a universal mechanism. This study thus revealed a key genetic mechanism underlying balancing crop yield and environmental stress resistance at a genome-wide level, and provided a large number of valuable IR loci for breeding new maize varieties with both high yield and stress tolerance via genetic engineering approaches in the future.