In　recently　years,　an　increasing　number　of　quaternary　ammonium　compounds　(QACs)　enter　waster　wastewater　treatment　plants　(WWTPs),　and　coexist　with　the　environmental　antibiotics　in　WWTPs.　In　this　study,　dodecyl　trimethyl　ammonium　chloride　(ATMAC-C12),　dodecyl　benzyl　dimethyl　ammonium　chloride　(BAC-C12)　and　didodecyl　dimethyl　ammonium　chloride　(DADMAC-C12)　were　added　to　nitrifying　system　treating　sewage　containing　environmental　concentration　of　ciprofloxacin　(CIP)　(0.2　mg/L),　respectively,　to　explore　the　different　responses　of　resistance　genes　(RGs)　under　the　co-occurrence　of　different　kinds　of　QACs　and　CIP　in　nitrifying　system.　Results　showed　that　partial　nitrification　was　achieved　by　QACs　and　CIP　co-loading,　and　the　cooccurrence　of　ATMAC-C12　and　CIP　had　more　serious　inhibitory　in　the　ammonia　oxidation　activity,　functional　genes,　extracellular　polymeric　substances　(EPS),　and　bacterial　community　structures　than　BAC-C12　and　DADMAC-C12　in　nitrifying　system.　Moreover,　the　co-occurrence　of　ATMAC-C12　and　CIP　stimulated　the　proliferation　of　more　intracellular　RGs　in　sludge　(si-RGs),　while　more　extracellular　RGs　in　sludge　(se-RGs)　and　RGs　in　water　(w-RGs)　were　enriched　under　the　co-occurrence　of　DADMAC-C12　and　CIP.　Mobile　genetic　elements　(MGEs)　cooperated　with　bacteria　to　alter　the　profiles　of　RGs.　Partial　least-squares　path　model　further　confirmed　that　MGEs　had　positive　effects　on　the　proliferation　and　transmission　of　si/se/w-RGs　(2　=　0.647,　0.918　and　0.627),　and　EPS　had　a　most　important　effect　(2　=　1.163)　on　the　w-RGs　under　the　co-occurrence　of　QACs　and　CIP.　Therefore,　it　should　pay　attentions　to　the　consumptions　of　QACs,　and　avoid　the　proliferation　and　transmission　of　RGs　caused　by　the　co-occurrence　of　QACs　and　environmental　antibiotics.