A　novel　series　of　2,3-dihydro-[1,4]dioxino[2,3-f]quinazoline　derivatives　were　designed,　synthesized　and　evaluated　as　reversible　and　noncovalent　epidermal　growth　factor　receptor　(EGFR)　inhibitors.　Most　of　the　compounds　exhibited　good　potency　against　EGFR(wt)　and　some　showed　moderate　to　excellent　potency　against　EGFR(T790M/L858R)　mutant.　The　half-maximal　inhibitory　concentration　(IC50)　values　of　twenty-one　compounds　against　EGFR(wt)　were　less　than　50　nM,　and　those　of　six　compounds　were　less　than　10　nM.　The　IC50　values　of　eleven　compounds　against　EGFR(T790M/L858R)　were　less　than　100　nM.　Among　these,　compound　b1　displayed　the　most　potent　inhibitory　activity　against　EGFR(wt)　(IC50　=　2.0　nM)　and　EGFR(T790M/L858R)　(IC50　=　6.9　nM).　Compounds　with　excellent　inhibitory　activities　against　EGFR(wt)　and　EGFR(T790M/L858R)　kinase　inhibitory　activities　showed　good　antiproliferative　activities　against　H358　and　A549　cells.　Docking　study　was　performed　to　position　compound　b1　into　the　EGFR　active　pocket　to　determine　the　probable　binding　conformation.　(C)　2016　Elsevier　Ltd.　All　rights　reserved.