A periodic density functional theory study of the sulfur vacancy formation mechanism on different edges of MoS2 nanocrystallites was investigated from thermodynamics and kinetics points of views. Thermodynamics study shows that the generations of vacancies on the Mo edge and basal plane were found severely inhibited by the thermodynamic limitations. Whilst the formation on the S edge can be proceeded spontaneously. Homolysis dissociation of H-2 molecule was found more favorable than heterolytic dissociation on sulfur edge. The process of dissociated H atoms to form absorbed H2S was proved to be the rate controlling step. By comparing the distribution of charges and FuKui function before and after the vacancy formation, the contribution of sulfur vacancy to electrophilicity of Mo was clear, sulfur vacancies formed at the edges of Mo and S is favorable to the following hydrodesulfurization (HDS) reactions, whereas, the generation of sulfur vacancies on the basal plane inhibits the chemical reaction. The findings are critical to the development of highly active HDS catalysts. (C) 2018 Elsevier Ltd. All rights reserved.