The　wastewater　containing　high　quaternary　ammonium　compounds　(QACs)　concentrations　from　hospitals　and　other　sources　may　cause　the　transient　shock　loads　on　the　wastewater　treatment　plants　(WWTPs).　Denitrification　is　the　key　part　of　nitrogen　removal　from　wastewater,　however,　the　effects　of　QACs　on　the　denitrification　and　the　spread　patterns　of　intracellular　and　extracellular　resistance　genes　were　still　unknown.　The　short-term　stress　of　three　frequently　detected　QACs　on　denitrification　were　systematically　investigated　in　this　study.　The　inhibitory　effect　on　nitrate　removal　had　the　following　rules:　BAC　C12　＞　ATMAC　C12　＞　DADMAC　C12.　The　inhibition　of　QACs　on　denitrification　performance　was　correlated　with　the　reduction　of　Thauera　abundance,　and　a　higher　QACs　concentration　made　stronger　inhibitory　effect.　Moreover,　high　concentrations　of　QACs　could　cause　a　significant　decrease　in　reactive　oxygen　species,　inhibit　cell　activity　and　extracellular　polymeric　substances　secretion.　Furthermore,　QACs　stimulated　an　overall　increase　of　intracellular　and　extracellular　QACs　resistance　genes　in　denitrification　systems,　both　in　sludge　and　in　water.　And　co-selection　among　resistance　genes　occurred　under　shock　loads　of　QACs,　especially　a　high　BAC　C12　concentration　caused　a　substantial　raise　in　abundances　of　resistance　genes　in　water.　It　was　worth　noting　that　resistance　genes　in　sludge　and　water　were　mainly　contributed　by　different　bacteria.　Rhizobium　and　Pseudomonas　may　be　the　potential　hosts　contributed　to　resistance　genes　in　sludge　while　Thauera　mainly　contributed　to　that　in　water.