Two dimensional molybdenum disulfide (2D-MoS2) has been recently developed to be used as superb adsorbents for removing heavy metals from water due to its huge sulfur-rich surface area. In this work, single adsorption and co-adsorption performances of H2O, Hg2+ and O-2 on MoS2 surface with and without S-vacancy defects have been theoretically studied to explore the Hg2+ adsorption and surface oxidation through density function theory (DFT) calculations. Moreover, the Hg2+ adsorption and surface oxidation have experimentally studied through atomic force microscopy (AFM) to verify the theoretical calculation results. It has been found that S-vacancy defects make MoS2 surface more reactive, leading to the much stronger adsorption energy of H2O, Hg2+ and O-2 on defective MoS2 surface. O-2 can only be physically adsorbed on the perfect MoS2 surface, while it bonds to the unsaturated Mo atoms at the vacancy site on defective MoS2 surface. Besides, co-adsorption results illustrate that Hg2+ have priority to react with MoS2 surface than O-2 due to the much stronger binding affinity, and surface oxidation occurs only when there are enough reaction sites for the Hg2+ adsorption and surface oxidation simultaneously. These theoretical co-adsorption results are consistent with the experimental Hg2+ adsorption and surface oxidation results obtained by AFM. These findings in this study are of great significance for the development and utilization of MoS2-based nanomaterials as a heavy metal adsorbent.