The Sansha Yongle Blue Hole is the world's deepest (301 m) underwater cave and has a sharp redox gradient, with oligotrophic, anoxic, and sulfidic bottom seawater. In order to discover the microbial communities and their special biogeochemical pathways in the blue hole, we analyzed the 16S ribosomal RNA amplicons and metagenomes of microbials from seawater depths with prominent physical, chemical, and biological features. Redundancy analysis showed that dissolved oxygen was the most important factor affecting the microbial assemblages of the blue hole and surrounding open sea waters, and significantly explained 44.7% of the total variation, followed by silicate, temperature, sulfide, ammonium, methane, nitrous oxide, nitrate, dissolved organic carbon, salinity, particulate organic carbon, and chlorophyll a. We identified a bloom of Alteromonas (34.9%) at the primary nitrite maximum occurring in close proximity to the chlorophyll a peak in the blue hole. Genomic potential for nitrate reduction of Alteromonas might contribute to this maximum under oxygen decrease. Genes that would allow for aerobic ammonium oxidation, complete denitrification, and sulfuroxidization were enriched at nitrate/nitrite-sulfide transition zone (90 and 100 m) of the blue hole, but not anammox pathways. Moreover, γ-Proteobacterial clade SUP05, ε-Proteobacterial genera Sulfurimonas and Arcobacter, and Chlorobi harbored genes for sulfur-driven denitrification process that mediated nitrogen loss and sulfide removal. In the anoxic bottom seawater (100-300 m), high levels of sulfate reducers and dissimilatory sulfite reductase gene (dsrA) potentially created a sulfidic zone of ~200 m thickness. Our findings suggest that in the oligotrophic Sansha Yongle Blue Hole, o 2 deficiency promotes nitrogen-and sulfur-cycling processes mediated by metabolically versatile microbials. O 2-deficient regions occur throughout global oceans 1. Intermediate layers of the ocean develop O 2-deficient water masses, referred to as oxygen minimum zones (OMZs), due to limitation in photosynthetic O 2 production and high-level aerobic respiration during the degradation of surface-derived organics 2. In these OMZs, such as the Eastern Tropical South Pacific (ETSP) and the Arabian Sea, O 2 concentrations fall below sensor-specific detection limits 3-5. In contrast, the Peru Upwelling Region, the Namibian Shelf, and the Indian Continental Shelf experience episodic plumes of hydrogen sulfide (H 2 S) 6-8. These sulfidic environments are also found in enclosed or semi-enclosed basins, including the Black Sea Basin 9-12 , the Baltic Sea Basin 13-15 , the Cariaco Basin 16,17 , and submarine caves, such as the Bahamian blue holes 18 , the Belize Blue Hole 19 , and the Sansha Yongle Blue Hole 20. In O 2-deficient regions, microbial reactions control key steps in carbon, nitrogen, and sulfur transformation under successional redox gradients extending throughout the water column 21. NO 3 − is the most energetically