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<i>Natronorubrum daqingense</i> JX313^T is an extremely halophilic archaea that can grow in a NaCl-saturated environment. The excellent salt tolerance of <i>N. daqingense</i> makes it a high-potential candidate for researching the salt stress mechanisms of halophilic microorganisms from <i>Natronorubrum</i>. In this study, transcriptome analysis revealed that three genes related to the biosynthesis of vitamin B₁₂ were upregulated in response to salt stress. For the wild-type (WT) strain JX313^T, the low-salt adaptive mutant LND5, and the vitamin B₁₂ synthesis-deficient strain Δ<i>cobC</i>, the exogenous addition of 10 mg/L of vitamin B₁₂ could maximize their cell survival and biomass in both optimal and salt stress environments. Knockout of <i>cobC</i> resulted in changes in the growth boundary of the strain, as well as a significant decrease in cell survival and biomass, and the inability to synthesize vitamin B₁₂. According to the HPLC analysis, when the external NaCl concentration (<i>w</i>/<i>v</i>) increased from 17.5% (optimal) to 22.5% (5% salt stress), the intracellular accumulation of vitamin B₁₂ in WT increased significantly from (11.54 ± 0.44) mg/L to (15.23 ± 0.20) mg/L. In summary, <i>N. daqingense</i> is capable of absorbing or synthesizing vitamin B₁₂ in response to salt stress, suggesting that vitamin B₁₂ serves as a specific compatible solute effector for <i>N. daqingense</i> during salt stress.