A series of novel quinolone derivatives ( 8a – j ) were synthesized, and their anticancer activities were tested in human cancer cell lines, human lung carcinoma cell (A549), human promyelocytic leukemia cell (HL-60), and human cervical cancer cell (Hela). Compound 8i was found to be 5-times more potent in cell-killing activity for cell lines A549, HL-60, and Hela than the positive control irinotecan or cisplatin, with IC₅₀ of 0.009, 0.008 and 0.010 µM, respectively. The docking study revealed that compound 8i might have strong interactions with the active site of DNA-topoisomerase I.