The microstructure, nucleation and growth of MgSO4 product layer during the reaction of MgO single crystal with SO2 and O2 were investigated with thermo gravity analyzer (TGA) and atomic force microscopy (AFM). The AFM images indicated that three dimensional islands with different sizes were formed during the initial reaction stage. At the initial stage, cone-shaped islands were formed, and most of them appeared at the position with terrace-step-kink. With the reaction time increasing, small islands would grow to large islands, and the coalescent would happen during this growth stage. During the product layer growth stage, the space and surface between islands would be occupied by islands, and continuum islands were formed. With the reaction time increasing in the product layer growth stage, the size of island increased while the number and total surface of all islands decreased. The microstructure, nucleation and growth of MgSO4 product layer during the reaction of MgO single crystal with SO2 and O2 were investigated with thermo gravity analyzer (TGA) and atomic force microscopy (AFM). The AFM images indicated that three dimensional islands with different sizes were At the initial stage, cone-shaped islands were formed, and most of them appeared at the position with terrace-step-kink. With the reaction time increasing, small islands would grow to large islands, and the coalescent would happen during this growth stage. the product layer growth stage, the space and surface between islands would be occupied by islands, and continuum islands were formed. With the reaction time increasing in the product layer growth stage, the size of island increased while the number and total surface of all islands decreased.