Two-dimensional (2D) conductive metal-organic frameworks (MOFs) were an emerging class of potential oxygen reduction reaction (ORR) electrocatalysts to replace platinum-containing electrode materials. Herein, by first -principles calculations, we systematically studied the structural stability, electronic properties and ORR catalytic activity of metal-hexahydroxybenzene nanosheets, M-3(C6O6), M = 3d and 4d transition metals. Based on formation energy, phonon spectrum and ab-initio molecular dynamics analyses, eight monolayer M3(C6O6) (M = Cr, Mn, Fe, Co, Cu, Zn, Ru and Rh) show superior thermodynamic, kinetic and thermal stabilities. Further ORR catalytic activity evaluation shown Cu-3(C6O6) and Rh-3(C6O6) had promising applications in catalyzing ORR 4e(-)pathway, with limiting potentials 0.76 and 0.80 V, respectively. The linear relationship between integrated crystal orbital Hamilton population (ICOHP) and delta G(OH* )explains the suitable adsorption energy of OH* on the catalyst, resulting in the excellent ORR activity of Cu3(C6O6) and Rh3(C6O6). Our study on M-3(C6O6) provides references for the research of other 2D MOFs as ORR catalysts.