Acid oxidative pressure leaching is a cost-effective way for recovering gold from refractory gold ores such as gold-bearing pyrite, yet our knowledge of the dissolution, crystallization, and phase transformation during pressure leaching is still controversial. This is partially due to the lack of thermodynamic data and in situ studies of the leaching process. Here, we combine thermodynamic modelling and in situ powder X-ray diffraction (PXRD) to investigate mineralogical phase changes during oxidation of pyrite. The polyhedron method has been utilised to estimate the standard Gibbs free energy of formation (∆Gfo) and enthalpy of formation (∆Hfo) of 31 sulphate minerals from 25 °C to 300 °C. The calculated thermodynamic data for the sulphate minerals agree well with the literature, with an average relative error of 0.23% for both ∆Gfo and ∆Hfo demonstrating the reliability of the polyhedron method. Some new thermodynamic data for the mineral phases at elevated temperature was calculated and used to construct the Eh-pH diagrams for the Fe-S-H2O system at 225 °C, which were used to predict phase transformations and chemical reactions during oxidation of pyrite. Based on the analysis of thermodynamic diagrams, the formation of basic ferric sulphate (BFS: Fe(OH)SO4) is favoured at stronger acidic and higher solution redox potential conditions, while hematite and FeSO4∙H2O occur at low solution redox potential conditions. These predictions agreed with the results from laboratory-based in situ PXRD experiments, in which the mineralogical phase transformations were studied during acid pressure treatment of pyrite in a capillary. The influence of initial concentration of ferric ions on the change of mineral phase was revealed. The results confirmed the formation of FeSO4∙H2O and Fe(OH)SO4 phases during the heating (24–225 °C) and annealing stages. These phases may passivate pyrite surface and hence slow down further pyrite oxidation but were re-dissolved during the annealing and/or cooling stages, depending on the initial concentration of ferric ions.