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<i>Deinococcus radiodurans</i> adapts to challenging environments by modulating gene expression in response to oxidative stress. Recently, bacterial small noncoding RNAs (sRNAs) have been presumed to participate in the transcriptional or translational regulation of stress-responsive genes. We found 24 sRNAs that may be involved in the oxidative stress response of <i>D. radiodurans</i> by deep RNA sequencing. Moreover, a typical stress-inducible sRNA, IGR_3053, named OsiA, was predicted to bind to the mRNA of <i>katA</i>, <i>katE</i>, and <i>sodC</i> by the bioinformatics method. An <i>osiA</i> knockout of <i>D. radiodurans</i> displayed increased sensitivity to H₂O₂ and the decreased catalase activity and total antioxidant activity, suggesting that OsiA probably serves as a regulator in the adaptation to oxidative environments. Further microscale thermophoresis results demonstrated that OsiA can directly bind to the mRNA of <i>katA</i>, <i>sodC</i>, and <i>katE</i>. The stability test result of <i>katA</i> mRNA showed that its half-life was 2 min in the <i>osiA</i> mutant compared with 5 min in the wildtype(wt) strain. Our results indicated that OsiA can enhance the stability of <i>katA</i> mRNA and the activity of KatA and consequently the oxidation resistance of <i>D.radiodurans</i>. We are the first one to explore the super-strong oxidative stress resistance of <i>D.radiodurans</i> at the level of post-transcriptional regulation, and found a new pathway that provides a new explanation for the long-term adaptability of <i>D.radiodurans</i> in extreme environments.