The simplest system where the microscopic physical nature of thermodiffusion can be understood theoretically is a binary mixture. The case of a liquid mixture is considered here, starting from the equilibrium state such as described by thermodynamics. Under a uniform temperature, gradients of composition and/or pressure bring about a non-equilibrium state where local enthalpy is not minimum and/or local entropy is not maximum. The gradients of enthalpy and entropy define a thermodynamic force which is shown to drive composition and pressure diffusions. The thermodynamic force considered in this paper has the physical dimension of a force, it is defined per particle, it is invariant under gauge transformations of enthalpy and entropy and lastly it obeys Newtonʼs third law. Under a non-uniform temperature, it is shown that such a thermodynamic force does not account for thermodiffusion. The thermodiffusive force is of a non-thermodynamic essence. The kinetic-theory account of the transport coefficients is examined in mixtures of long macromolecules with small solvent molecules.