The atomic size factors for Al, Sc and Ca are calculated in Mg-based substitutional solid solution from first-principles calculation as a first step of searching most effective solute element for the solid-solution strengthening. The atomic size factor for Al is -12.4% that is in a good agreement with experimental result. The atomic size factor for Ca and Sc is found to be +20.4% and +3.3%. The absolute value of atomic size factor for Ca is lager than that for Al. Mg-Ca system is expected to be significant solid solution strengthening. Additionally, the misfit strain is calculated from the distortion of atomic positions in order to compare with the atomic size factors.