Minimal　study　focused　on　the　association　between　mixed　pollutants　in　atmospheric　particulate　matter　(PM2.5)　and　their　reproductive　health　risks.　Utilizing　a　novel　quantitative　structure-activity　relationship　(QSAR)　integrated　machine　learning　algorithms,　we　evaluated　the　mixed　reproductive　health　risks　associated　with　phthalates　(PAEs)　and　organophosphates　(OPEs)　exposure　by　assessing　the　affinities　of　these　compounds　binding　to　estrogen　receptors　(ER)　and　androgen　receptors　(AR).　The　mixed　toxicity　equivalent　factor　(TEFmix)　and　mixed　toxicity　equivalent　quantity　(TEQmix)　by　the　QSAR　model　were　all　smaller　than　the　sum　TEF　and　TEQ　of　individual　PAEs　and　OPEs,　which　may　be　due　to　the　antagonistic　effect　of　PAEs　and　OPEs　monomers　on　reproductive　toxicity.　Based　on　network　toxicology　approach,　a　total　of　590　potential　targets　associated　with　PAEs　and　OPEs　affecting　sex　hormones　were　initially　identified,　with　an　additional　50　core　targets,　including　AR　and　ER.　Di-2-ethylhexyl　phthalate　(DEHP),　triphenyl　phosphate　(TPHP)　and　mono-(2-ethylhexyl)　phthalate　(MEHP)　were　key　components　to　disrupt　AR　and　ER　signaling　pathway,　and　was　confirmed　by　molecular　docking　analysis.　In　addition　to　ER　and　AR,　serine/threonine　kinase　1　(AKT1)　and　heat　shock　protein　90　alpha　family　A　member　1　(HSP90AA1)　might　be　key　targets　for　reproductive　toxicity,　which　have　hardly　mentioned　before.　Our　study　provided　precious　information　on　the　mixed　reproductive　exposure　risk　of　PAEs　and　OPEs　in　PM2.5,　and　innovatively　explored　the　potential　mechanisms　of　PAEs　and　OPEs　affecting　human　reproductive　health　using　network　toxicology.