Background:　Epidermal　growth　factor　receptor　(EGFR)　is　a　validated　and　therapeutically　amenable　target,　and　inhibition　of　the　EGFR　signaling　pathway　has　emerged　as　an　attractive　target　for　cancer　therapy.Methods:　The　present　work　was　designed　to　synthesize　and　evaluate　the　antiproliferative　activity　of　a　novel　series　of　3,9-dioxatetraasteranes　as　potential　inhibitors　of　EGFR.　All　target　compounds　were　evaluated　for　antiproliferative　activity　in　vitro　against　A549　and　HepG2　cell　lines.Results:　Among　the　target　compounds,　compound　B13　displayed　the　most　potent　antiproliferative　activity　against　A549　with　IC50　=　4.31　mu　M　and　HepG2　with　IC50　=　6.92　mu　M.　In　addition,　a　molecular　docking　study　was　performed　to　investigate　the　binding　mode　and　binding　capacity　with　EGFR　(PDB　code:　1M17).Conclusion:　The　results　indicated　that　3,9-dioxatetraasteranes　may　be　promising　potential　EGFR　inhibitors.