Characterizing thermal diffusion processes caused by a temperature gradient in binary mixtures is difficult. The classic theory employed to interpret the experimental data does not fully explain the physical meaning of the Soret coefficient and its sign change. In this study, a new thermal diffusion equation is derived based on thermal dynamic theory. The new equation relates thermal diffusion to the net molecular interaction energy of the components in a mixture. It was also demonstrated that the Soret coefficient is a simple function of the difference between the enthalpy of a component in the mixture and its enthalpy at reference state in the mixture. Theoretical analysis of experimental data obtained by other researchers shows that the new equations quantitatively explain the influence of molecular interactions on the Soret effect. Additionally, they qualitatively explain why the Soret coefficient changes its sign as molar fraction increases from 0 to I in the mixtures.