Abstract: Eighteen novel ciprofloxacin-histone deacetylase inhibitor (HDACi) conjugates were designed and synthesized from suberic acid and ciprofloxacin via esterification and amidation reaction. All conjugates were confirmed by the application of ¹H NMR and HR-MS spectra, their activities against HDACs were evaluated by HDACs assay kit and the anti-tumor activities were evaluated in five cancer cells with CCK-8 assay. The preliminary biological results showed that these conjugates displayed potent activity against HDACs and significant anti-proliferative effect on the cancer cells. Some conjugates exhibited activities better than that of the parent compound ciprofloxacin and drug SAHA. Specifically, compound 12b exhibited the most potent anti-HDAC1 (IC₅₀=0.041±0.005 μmol·L^-1) and HDAC6 (IC₅₀=0.039±0.006 μmol·L^-1) activities, and also showed the greatest potency against NCI-H460 (IC₅₀=0.7±0.04 μmol·L^-1) and A549 (IC₅₀=0.9±0.12 μmol·L^-1). These results suggest that the histone deacetylase inhibitors have significant anti-tumor activities, which can enhance the anti-tumor activity of quinolones.