Hydrogen　sulfide　(H2S),　as　a　key　gas　signaling　molecule,　plays　an　important　role　in　regulating　various　diseases,　with　appropriate　concentrations　providing　antioxidative,　anti-inflammatory,　and　anti-apoptotic　effects.　The　specific　role　of　H2S　in　acute　hypoxic　injury　remains　to　be　clarified.　This　study　focuses　on　the　H2S　donor　sodium　hydrosulfide　(NaHS)　and　explores　its　protective　effects　and　mechanisms　against　acute　hypoxic　lung　injury.　First,　various　mouse　hypoxia　models　were　established　to　evaluate　H2S＇s　protection　in　hypoxia　tolerance.　Next,　a　rat　model　of　acute　lung　injury　(ALI)　induced　by　hypoxia　at　6500　m　above　sea　level　for　72　h　was　created　to　assess　H2S＇s　protective　effects　and　mechanisms.　Evaluation　metrics　included　blood　gas　analysis,　blood　routine　indicators,　lung　water　content,　and　lung　tissue　pathology.　Additionally,　LC-MS/MS　and　bioinformatic　analyses　were　combined　in　performing　quantitative　proteomics　on　lung　tissues　from　the　normoxic　control　group,　the　hypoxia　model　group,　and　the　hypoxia　model　group　with　NaHS　treatment　to　preliminarily　explore　the　protective　mechanisms　of　H2S.　Further,　enzyme-linked　immunosorbent　assays　(ELISA)　were　used　to　measure　oxidative　stress　markers　and　inflammatory　factors　in　rat　lung　tissues.　Lastly,　Western　blot　analysis　was　performed　to　detect　Nrf2,　HO-1,　P-NF-kappa　B,　NF-kappa　B,　HIF-1　alpha,　Bcl-2,　and　Bax　proteins　in　lung　tissues.　Results　showed　that　H2S　exhibited　significant　anti-hypoxic　effects　in　various　hypoxia　models,　effectively　modulating　blood　gas　and　blood　routine　indicators　in　ALI　rats,　reducing　pulmonary　edema,　improving　lung　tissue　pathology,　and　alleviating　oxidative　stress,　inflammatory　responses,　and　apoptosis　levels.