Both　c-Met　and　VEGFR-2　were　important　targets　for　cancer　therapies.　In　order　to　develop　reversible　and　non-covalent　c-Met　and　VEGFR-2　dual　inhibitors,　a　series　of　[1,4]　dioxino[2,3-f]　quinazoline　derivatives　were　designed　and　synthesized.　The　enzyme　assay　demonstrated　that　most　target　compounds　had　inhibition　potency　on　both　c-Met　and　VEGFR-2　with　IC50　values　in　nanomolar　range　especially　compounds　7m　and　7k.　Based　on　further　cell　proliferation　assay　in　vitro,　compound　7k　showed　significantly　anti-tumor　activity　in　vivo　on　a　hepatocellular　carcinoma　(MHCC97H　cells)　xenograft　mouse　model.　We　docked　the　compound　7m　with　c-Met　and　VEGFR-2　kinases,　and　interpreted　the　SAR　of　these　analogues.　All　results　indicated　that　the　target　compounds　were　dual　inhibitors　of　c-Met　and　VEGFR-2　kinases　that　held　promising　potential　in　cancer　therapy.