Benzethonium　chloride　(BZC)　and　methylparaben　(MeP)　are　commonly　added　into　cosmetics　as　preservatives,　which　are　frequently　detected　in　wastewater　treatment　plants.　Different　response　patterns　of　denitrification　system　were　proposed　under　single　and　combined　exposure　to　BZC　and　MeP　(0,　0.5,　5　mg/L)　by　evaluating　system　performance,　functional　genes,　extracellular　polymeric　substance　(EPS),　cytotoxicity,　microbial　community　structure　and　resistance　genes　(RGs).　The　inhibition　effect　of　BZC　on　denitrification　system　was　stronger　than　MeP,　and　the　co-exposure　of　BZC　and　MeP　showed　synergistic　effect,　enhancing　the　inhibition　effect　of　BZC　single　exposure.　BZC　and/or　MeP　could　promote　the　diffusion　of　RGs　in　sludge,　including　intracellular　RGs　(si-RGs)　and　extracellular　RGs　(se-RGs).　Moreover,　the　single　exposure　of　BZC　and　co-exposure　of　BZC　and　MeP　increased　the　dissemination　risks　of　RGs　in　water　(w-RGs).　IntI1　and　tnpA-04,　mobile　genetic　elements　(MGEs),　correlated　positively　with　diverse　RGs　from　different　fractions.　Notably,　the　spread　of　RGs　through　horizontal　gene　transfer　mediated　by　MGEs　and　the　flow　of　si-RGs　into　extracellular　and　water　were　observed　in　this　study.　©　2024　Elsevier　B.V.