Background:As was reported, gefitinib (Iressa ® ) showed a strong growth inhibitory effect on non-small-cell lung cancer PC-9 cells with mutant EGFR, but did not so much on A549 cells with wild-type EGFR. Observation:We here demonstrated by isobolograms and combination index analyses that the paired combinations of gefitinib with flavonoids from Wogon (Scutellaria baicalensis root): wogonin, oroxylin A and chrysin exerted synergistic anti-tumor effects against A549 cells. Result:The cell cycle analyses revealed that the combination of gefitinib and oroxylin A in A549 cells induced more apoptotic cells than other paired combinations as well as gefitinib alone. Thus, it is anticipated that oroxylin A could help to enhance the remission rate in the gefitinib therapy for the patients with non-small cell cancer cells with wild-type EGFR which provide a poor prognosis. Conclusion:Since the Wogon flavonoids, wogonin, oroxylin A and chrysin, accelerated the acetylation of Lysine residues of histone proteins, it is suggested that they put forth anti-tumor activities through inhibition of histone deacetylases which mediated the post-translational modification of histones.