The　effects　of　different　concentrations　of　perfluorooctane　sulfonate　(PFOS)　on　the　viability　of　A549　cells　were　determined　by　the　CCK-8　method.　The　effects　of　PFOS　exposure　on　miRNAs　expression　in　A549　cells　were　detected　by　the　next-generation　sequencing　method　to　investigate　the　molecular　mechanism　of　pulmonary　toxicity　caused　by　PFOS.　Target　genes　with　abnormal　expression　of　miRNAs　were　predicted,　and　their　involved　signaling　pathways　and　potential　biological　functions　were　inferred　through　bioinformatics　analysis.　The　results　showed　that　a　low　concentration　of　PFOS　(＜200μmol/L)　promoted　the　proliferation　of　A549　cells,　while　a　high　concentration　of　PFOS　inhibited　the　proliferation　of　A549　cells.　The　expression　levels　of　108　miRNAs　and　63　miRNAs　in　A549　cells　exposed　to　300　μmol/L　PFOS　for　24　h　were　significantly　up-regulated　and　down-regulated.　Differentially　expressed　miRNAs　participate　in　biological　processes　such　as　cell　proliferation,　metabolic　process,　and　developmental　process　through　signaling　pathways　such　as　Ras,　Rap1,　HIF-1,　ErbB,　VEGF　and　so　on.　This　study　suggested　that　PFOS　can　threaten　the　lung　by　affecting　cell　proliferation　and　inducing　inflammation.　©　2021,　Editorial　Board　of　China　Environmental　Science.　All　right　reserved.