A series of novel 7-(4-alkoxyimino-3-hydroxypiperidin-l-yl)quinolone derivatives were designed, synthesized and evaluated for in vitro antibacterial activities. Compounds 8f, 8g, 8i and 8j with the potencies similar to or better than those of levofloxacin and IMB against Staphylococcus aureus and Staphylococcus epidermidis, worth further investigation.