The tensile behavior of γ-TiAl alloys with vacancy defects has been studied by molecular dynamics (MD) simulation considering different lattice orientations. A succession of simulations were performed to analyze the effect of vacancy and lattice orientation on mechanical properties and micro-defect evolution. The results indicate that the orientation has evident impacts on critical stress with Ti and Al vacancy. The yield stress of the model with Ti vacancy is higher than the model containing Al vacancy along three crystal directions. During the deformation of single crystal γ-TiAl alloys, it is found that the dislocation density has the same changeable trend as the number of stacking faults. In addition, the influence of temperature on yield strength also was discussed. The ultimate stress and elastic modulus decrease nonlinearly with the increasing of temperature. The higher temperature results in the less influence of crystal orientation and vacancy defect on the ultimate stress. Copyright © 2020, Northwest Institute for Nonferrous Metal Research. Published by Science Press. All rights reserved.