[Objective] To study the sulfur oxidation characteristics of Halothiobacillus diazotrophicus LS2 under different oxygen levels and to decipher the mechanism of strain LS2 adapting to low-oxygen environments. [Methods] The concentrations of S₂O₃^2- and SO₄^2- were measured by ion chromatography. Bacterial growth was determined by plate dilution coating method. The differentially expressed genes and related metabolic pathways were identified and analyzed by transcriptome sequencing and bioinformatics technology. [Results] Strain LS2 oxidized reduced sulfur compounds and grew under 0.2%–21.0% oxygen, and it maintained high sulfur oxidation activity under the oxygen level above 1.6%. Comparative transcriptomic analysis screened out 851 differentially expressed genes that might be related to the adaptation to low oxygen, including 464 up-regulated genes and 387 down-regulated genes. In sulfur metabolism, thiosulfate sulfurtransferase, sulfur oxidase/reductase, and sulfide: quinone oxidoreductase were up-regulated, while the Sox enzyme system was down-regulated, which indicated that strain LS2 might change the sulfur oxidation pathway to adapt to low-oxygen environment. In the low-oxygen group, the cbb₃-type cytochrome c oxidase was up-regulated to increase the O₂-binding efficiency. Meanwhile, since less electron could be received by O₂, the nitrogenase genes nifDKH and Fix complex genes fixA, fixB, fixC, fixX were up-regulated, making N₂ and CO₂ the alternative electron accepters to maintain redox balance, which explained the higher maximum bacterial growth in low-oxygen environments. [Conclusion] Strain LS2 is a sulfur-oxidizing bacterium that can maintain high sulfur oxidation activity in the low-oxygen environment. Sulfide: quinone oxidoreductase, high-oxygen-affinity terminal oxidases, and nitrogenase play a role in the adaptation to the low-oxygen environment. This study is of positive significance for deciphering the mechanism of sulfur oxidation under low oxygen and provides a theoretical basis for optimizing the treatment process of sulfur-containing wastewater.