Metal-organic frameworks (MOFs) receive more and more interest in the field of analytical chemistry for their diverse structures and multifunctionality. In this study, we have designed and fabricated nanoscale MOF-based nanoprobes for multicolor detection of DNA targets with improved sensitivity. To do so, MOF-based nanoprobes, constructed by using porous MOFs as a scaffold to load signal dyes and a DNA hairpin structure as capping shell, have been prepared. Once the target has been introduced, a competitive displacement reaction triggers the release of fluorophores from the MOFs' pores. Consequently, a significantly enhanced fluorescence signal can be observed owing to the high loading capacity of MOFs. Therefore, the stimuli-responsive nanoprobes can enable sensitive detection of DNA targets with a low detection limit of 20 fM and selective identification to discriminate single-base mismatch. Moreover, the MOFs can encapsulate different fluorophores with different DNA gatekeepers designed according to the sequence of the target DNA, resulting in more kinds of stimuli-responsive nanoprobes for multiplexed DNA analysis in the same solution. Furthermore, these smart nanoprobes reported in this paper may provide a unique MOF-based tool for detection of various targets via stimuli-responsive systems in the future to widen the applications of MOFs.