Epidermal　growth　factor　receptor　(EGFR)　is　the　most　attractive　target　for　drug　research　in　non-small　cell　lung　cancer　(NSCLC).　The　first-generation　EGFR　tyrosine　kinase　inhibitors　(TKIs)　Gefetinib　and　Elotinib　showed　good　clinical　efficacy　on　lung　adenocarcinoma　tumors,　but　almost　all　patients　developed　resistance　to　these　inhibitors　over　time.　Quinazoline　and　quinoline　derivatives　are　common　targeted　inhibitors　of　EGFR　kinase,　and　their　structural　optimization　is　an　important　direction　for　the　development　of　effective　targeted　anticancer　drugs.　Based　on　these　facts,　a　series　of　heterocyclic　2,3-dihydro-[1,4]dioxino[2,3-f]quinazoline　derivatives　have　been　designed　and　synthesized　and　their　structures　were　confirmed　by　spectral　analyses.　The　cytotoxic　activity　of　the　newly　synthesized　compounds　was　evaluated　against　the　human　kidney　epithelial　T293　cell　line,　normal　lung　cell　lines　WI-38,　non-small　cell　lung　cancer　A549　and　NCI-H157　cell　lines　using　MTT.　The　tested　compounds　showed　an　evident　anticancer　activity　against　the　tested　cell　lines,　especially　compound　13c,　which　was　the　most　potent　anticancer　agent　with　half　maximal　inhibitory　concentrations　(IC50)　between　8.82　and　10.24 μM.　Docking　study　showed　that　compound　13b　could　be　nicely　bound　to　the　ATP　binding　pocket　of　EGFR.　In　addition,　the　inhibitory　activity　of　the　target　compounds　against　epidermal　growth　factor　receptor　tyrosine　kinase　(EGFR-TK)　was　evaluated.　Results　indicated　the　ability　of　the　target　compounds　to　inhibit　EGFR-TK　with　half　maximal　inhibitory　concentrations　(IC50)　in　the　range　of　10.29 nM　to　652.3 nM.　In　view　of　the　reported　compound　activity,　the　structure　deserves　further　optimization　as　cancer　treatment　agents.