In this work, we theoretically investigated the friction mechanism of hexagonal MoS2 (a well-known lamellar compound) using a computational chemistry method. First, we determined several parameters for molecular dynamics simulations via accurate quantum chemistry calculations and MoS2 and MoS2-xOx structures were successfully reproduced. We also show that the simulated Raman spectrum and peak shift on X-ray diffraction patterns were in good agreement with those of experiment. The atomic interactions between MoS2 sheets were studied by using a hybrid quantum chemical/classical molecular dynamics method. We found that the predominant interaction between two sulfur layers in different MoS2 sheets was Coulombic repulsion, which directly affects the MoS2 lubrication. MoS2 sheets adsorbed on a nascent iron substrate reduced friction further due to much larger Coulombic repulsive interactions. Friction for the oxygen-containing MoS2 sheets was influenced by not only the Coulomb repulsive interaction but also the atomic-scale roughness of the MoS2/MoS2 sliding interface.