An efficient protocol for Ru(II)-catalyzed direct C-H oxygenation of a broad range of flavone and chromone substrates was developed. This convenient and powerful synthetic tool allows for the rapid installation of the hydroxyl group into the flavone, chromone, and other related scaffolds and opens the way for analog synthesis of highly potent Aurora kinase inhibitors. The molecular docking simulations indicate that the formation of bidentate H-bonding patterns in the hinge regions between the 5-hydroxyflavonoids and Ala213 was the significant binding force, which is consistent with experimental and computational findings.