Developing multifunctional metal-organic frameworks (MOFs) is a new research trend. MOFs have shown remarkable performances in both proton conduction and fluorescence sensing, but the MOFs integrating the two performances are scarce. Herein, a Co-MOF, [Co6(oba)4(Hatz)(atz)(H2O)2(μ3-OH)2(μ2-OH)]·H2O (1, H2oba = 4,4-oxybis(benzoic acid), Hatz = 5-amino-1H tetrazole), has been assembled by Co2+ ions with H2oba and Hatz ligands, providing a unique example of multifunctional MOFs with both proton conduction and fluorescence sensing performances. The framework of 1 displays a pillar-layer structure built by the oba ligand as a pillar and a layer composed of Co-clusters and atz linkers. Because large-scale single crystals of 1 were successfully synthesized, the proton conduction ability of 1 was investigated using single crystal samples. 1 exhibits highly anisotropic conduction with conductivity values of 1.1 × 10-3 S cm-1 along the [001] direction and 9.1 × 10-6 S cm-1 along the [010] direction at 55 °C and 95% RH, respectively. Meanwhile, the fluorescence sensing of 1 towards metal ions was studied in aqueous solutions. Attractively, 1 may sensitively and selectively detect Fe3+ ions in the presence of other interfering ions by fluorescence quenching.