As an important subclass of MOFs, ZIF-8, built from 2-methylimidazole and Zn(NO3)2·6H2O, possesses excellent biocompatibility and high stability in aqueous solution. Recently, it has been found that ZIF-8 can efficiently adsorb DNA and quench the adsorbed fluorophores to a large extent. These properties make it possible to prepare DNA-based optical sensors using ZIF-8. Although practical analytical applications are being demonstrated, the basic understanding of the binding between ZIF-8 and DNA in solution has received relatively little attention. In this work, we report that the adsorption of 12-, 18-, 24-, and 36-mer single-stranded DNAs on ZIF-8 are affected by several factors. It is found from the outcomes that shorter DNAs are adsorbed more rapidly to the surface of ZIF-8. On the other hand, desorption of the probe DNA can be achieved using complementary strand DNA to restore the fluorescence value. Furthermore, the salt contributes to adsorption to some extent. These findings are important for further understanding of the interactions between DNA and ZIF-8 and for the optimization of DNA and MOF-based devices and sensors.