Abstract: A new method for the prediction of Gibbs free energies of formation for hydrated clay minerals is proposed based on the parameter ΔGO= Mz+(clay) characterizing the oxygen affinity of the cation Mz+. The Gibbs free energy of formation from constituent oxides is considered as the sum of the products of the molar fraction of an oxygen atom bound to any two cations multiplied by the electronegativity difference defined by the ΔGO= Mz+(clay) between any two consecutive cations. The ΔGO= Mz+(clay) value, using a weighting scheme involving the electronegativity of a cation in a specific site (interlayer, octahedral, or tetrahedral) is assumed to be constant and can be calculated by minimization of the difference between experimental Gibbs free energies (determined from solubility measurements) and calculated Gibbs free energies of formation from constituent oxides. Results indicate that this prediction method compared to other determinations, gives values within 0.5% of the experimentally estimated values. The relationships between ΔGO= Mz+(clay) corresponding to the electronegativity of a cation in either interlayer or octahedral sites and known ΔGO= Mz+(aq) were determined, thereby allowing the prediction of the electronegativity of transition metal ions and trivalent ions in hydrated interlayer sites and octahedral sites. Prediction of Gibbs free energies of formation of any clay mineral with various ions located in the interlayer and with different cations in octahedral sites is possible. Examples are given for Al-rich montmorillonite from Aberdeen, transition element-exchanged montmorillonite, and Ni-rich stevensite, and the results appear excellent when compared to experimental values.