Four new naphthoxazole compounds 1–4 have been synthesized and characterized. The DNA-binding was studied by absorption spectroscopy, viscosity measurements and luminescence spectra. The DNA binding constants were determined to be 5.06×10 3 for 1, 5.29×10 4 for 2, 3.58×10 3 for 3 and 7.75×10 3 M −1 for 4, respectively. The results show that these compounds can intercalate into the DNA base pairs. The stoichiometries of compound/DNA are 1:1 for 1, 2, 4, and 1.5:1 for 3. Interaction of compounds 1–4 with plasmid pBR322 DNA studied by gel electrophoresis experiments reveals that compounds can cleave pBR322 DNA upon irradiation or hydrolytic conditions. The antioxidant activities of these compounds against hydroxyl radical were also explored.