A DNA‐sensing platform is developed by exploiting the easy surface functionalization of metal–organic framework (MOF) particles and their highly parallelized fluorescence detection by flow cytometry. Two strategies were employed to functionalize the surface of MIL‐88A, using either covalent or non‐covalent interactions, resulting in alkyne‐modified and biotin‐modified MIL‐88A, respectively. Covalent surface coupling of an azide‐dye and the alkyne–MIL‐88A was achieved by means of a click reaction. Non‐covalent streptavidin–biotin interactions were employed to link biotin–PNA to biotin–MIL‐88A particles mediated by streptavidin. Characterization by confocal imaging and flow cytometry demonstrated that DNA can be bound selectively to the MOF surface. Flow cytometry provided quantitative data of the interaction with DNA. Making use of the large numbers of particles that can be simultaneously processed by flow cytometry, this MOF platform was able to discriminate between fully complementary, single‐base mismatched, and randomized DNA targets.