MicroRNAs (miRNAs) are a new class of small RNAs, which act as post-transcriptional negative regulators of gene expression. Plant miRNAs are important in the regulation of plant growth, development and in response to various abiotic and biotic stresses. miR398 is the first reported miRNA to be down-regulated by oxidative stresses. miR398 plays an impor-tant role in stresses, such as regulating copper homeostasis, in response to abiotic stresses including heavy metals, sucrose, and ozone and biotic stresses via down-regulating the expression of Cu/Zn-superoxide dismutase (CSD). This review fo-cused on the crucial role of miR398 in regulation of different stresses and the transcriptional regulation of MIR398 gene.