Deep hydrodesulfurization (HDS) is the key method for clean oil production to meet the strict environmental regulations. Density functional theory (DFT) was performed to provide theoretical insight into the influence of microwave electric field on the adsorption of H2 molecular and sulfur vacancy formation on different edges of MoS2 nanocrystallite. The influence of the electric field on the structure and electrical properties of MoS2 nanocrystallites with sulfur vacancies was also theoretically analyzed. It was found that electric field in a specific direction enhances the adsorption of H2 on the edge of MoS2 cluster. Its application also benefits the spontaneous formation of specific S vacancy on the S edge and increases the active site number of the cluster. The presented results would provide new insights into understanding the promotion mechanism of microwave on the HDS process.