The　role　of　estrogen　in　inducing　chemoresistance　is　not　yet　fully　understood.　The　objective　of　this　study　was　to　observe　the　relationship　between　estrogen　levels　and　cellular　response　to　chemotherapeutic　drugs　in　non-small　cell　lung　cancer　(NSCLC)　and　to　reveal　the　potential　mechanisms　involved.　Cell　viability　was　analyzed　after　pre-treating　NSCLC　cells　with　different　levels　of　estrogen　(E2),　followed　by　treatment　with　an　anti-tumor　drug　for　48　h.　The　roles　of　various　estrogen　receptors　(ERs)　were　examined　in　vitro　by　blocking　the　activity　of　each　ER　individually.　The　ER　pathway　was　further　confirmed　in　NSCLC　tissues.　It　was　found　that　10-1000　nM　E2　resulted　in　a　decreased　cellular　response　to　DDP　in　H1650　cells　compared　to　the　use　of　cisplatin　alone　(P　＜　0.05).　However,　this　result　was　not　demonstrated　in　H1299　cells,　which　lack　p53.　Both　ER　alpha　and　ER　beta　were　associated　with　E2-induced　cisplatin　chemoresistance,　though　they　had　opposite　functions.　p53　expression　did　not　correlate　with　the　expression　of　ER　alpha　or　ER　beta　individually.　However,　a　statistically　significant　correlation　between　p53　expression　and　ERa　to　ERb　mRNA　ratio　was　observed　(P　＜　0.001,　R　=　-0.676).　These　findings　suggest　that　E2-induced　DDP　chemoresistance　depends　on　the　balance　between　ER　alpha　and　ER　beta　expression　and　the　p53　pathway.