The composition and temperature dependences of site occupation for Al, Cr, W, and Nb in Mo Si2 are investigated by using a thermodynamics model and first principles calculations. A simple parameter measuring the substitution energy difference between Si and Mo sites reflects the nature of site occupancy. At 0 K, these elements prefer Si sites in Mo-rich and Mo sites in Si-rich, and show no site preference in stoichiometric Mo Si2. At elevated temperature, the site occupation behaviors show strong dependence on both composition and temperature. Some calculated results have been certified in previous experiments. The composition and temperature dependences of site occupation for Al, Cr, W, and Nb in Mo Si2 are investigated by using a thermodynamics model and first principles calculations. A simple parameter measuring the substitution energy difference between Si and Mo sites reflects the nature of site occupancy. At 0 K, these elements prefer Si sites in Mo-rich and Mo sites in Si-rich, and show no site preference in stoichiometric Mo Si2. At elevated temperature, the site occupation behaviors show strong dependence on both composition and temperature. Some calculated results have been certified in previous experiments.