The essential objective of this work is to establish the influence of grain size and thermo-mechanical conditions on the activation energy for super plastic flow (QSPF) in Ti-6Al-4V alloy by applying the quantum mechanics and relativistic model (QM-RM) proposed by Muñoz-Andrade, in the framework of the unified physics. The QM-RM allows the direct determination of the QSPF in advanced materials at instantaneous thermo-mechanical material working conditions. By applying, the QM-RM on the experimental results reported previously by some authors, it is shown for grain size of 6.1μm, that the calculated QSPF for grain boundary sliding is about 193 and 178 kJ/mol, at 850°C with an efficiency of power dissipation, η=0.65. These results are in closed agreement with the values of 204 and 174 kJ/mol reported previously for grain boundary self-diffusion energy of α-Ti. Nevertheless, for grain size of 0.6μm the calculated QSPF is 142 kJ/mol at 650°C, with an efficiency of power dissipation, η=0.61. As well, in order to understand the phenomenology and mechanics of SPF in Ti-6Al-4V alloy, the variation of the activation energy with the temperature; stress and strain rate is analyzed in association with coupled mechanisms during SPF, such as grain boundary sliding, cooperative grain boundary sliding and self-accommodation process related to the microstructure. In summary, the results of QSPF obtained in this work, by the QM-RM are in closed agreement with results reported previously by using the theoretical and conventional methodology set up by Mohamed and Langdon.