In this research, the effects of different parameters on simulation of Young’s modulus of a Graphene sheet are studied. In simulation of Young’s modulus of Graphene sheet, different parameters such as the thickness of a single layer of Graphene, type of loading and boundary conditions, effects of interactions non-neighbor atoms, type of element for carbon-carbon bond, mechanical properties of carbon-carbon bond and the size of the Graphene sheet influence the results. It was found that the thickness of a single layer Graphene and the type of element are effective parameters. Moreover, the type of loading and boundary conditions did not influence the Young’s modulus of the Graphene sheet. Therefore, the Graphene sheet can be considered as an isotropic material. Considering the effects of interactions of non-neighbor atoms increases the run-time and improves the accuracy of calculations. Mechanical properties of carbon-carbon bond are important parameters and must be chosen carefully. Also, it has been observed that when the length and width of the Graphene sheet are smaller than one nanometer, the size of Graphene sheet has a great influence on the Young’s modulus.