Background:　Persistent　organic　pollutants　(POPs)　are　persistent　in　the　environment　after　release　from　industrial　compounds,　combustion　productions　or　pesticides.　The　exposure　of　POPs　has　been　related　to　various　reproductive　disturbances,　such　as　reduced　semen　quality,　testicular　cancer,　and　imbalanced　sex　ratio.　Among　POPs,　dichlorodiphenyldichloroethylene　(4,4＇-DDE)　and　polychlorinated　biphenyls　(PCBs)　are　the　most　widespread　and　well-studied　compounds.　Recent　studies　have　revealed　that　4,4＇-DDE　is　an　antagonist　of　androgen　receptor　(AR).　However,　the　mechanism　of　the　inhibition　remains　elusive.　CB-153　is　the　most　common　congener　of　PCBs,　while　the　action　of　CB-153　on　AR　is　still　under　debate.　Results:　Molecular　docking　and　molecular　dynamics　(MD)　approaches　have　been　employed　to　study　binding　modes　and　inhibition　mechanism　of　4,4＇-DDE　and　CB-153　against　AR　ligand　binding　domain　(LBD).　Several　potential　binding　sites　have　been　detected　and　analyzed.　One　possible　binding　site　is　the　same　binding　site　of　AR　natural　ligand　androgen　5　alpha-dihydrotestosterone　(DHT).　Another　one　is　on　the　ligand-dependent　transcriptional　activation　function　(AF2)　region,　which　is　crucial　for　the　co-activators　recruitment.　Besides,　a　novel　possible　binding　site　was　observed　for　POPs　with　low　binding　free　energy　with　the　receptor.　Detailed　interactions　between　ligands　and　the　receptor　have　been　represented.　The　disrupting　mechanism　of　POPs　against　AR　has　also　been　discussed.　Conclusions:　POPs　disrupt　the　function　of　AR　through　binding　to　three　possible　biding　sites　on　AR/LBD.　One　of　them　shares　the　same　binding　site　of　natural　ligand　of　AR.　Another　one　is　on　AF2　region.　The　third　one　is　in　a　cleft　near　N-terminal　of　the　receptor.　Significantly,　values　of　binding　free　energy　of　POPs　with　AR/LBD　are　comparable　to　that　of　natural　ligand　androgen　DHT.