Pyrite depression with prolonged pre-conditioning treatment in high salinity water has attracted much of researchers’ interest in recent years considering the increased utilisation of multiple stage flotation, closed water circuits, clay minerals, and sea water in flotation plants. In this study, the role of calcium (Ca)/magnesium (Mg) precipitates in stabilising the dissociative ferric hydroxy-xanthate (FHX), and its effect on modifying the balance of hydrophobic/hydrophilic species on the pyrite surface were primarily investigated. The total amount of extractable Fe-bearing species on pyrite concentrates and tailings after floatability test was quantitively determined using ethylenediaminetetraacetic acid (EDTA) extraction tests combined with inductively coupled plasma optical emission spectroscopy (ICP-OES). A more evident accumulation of extracted-Fe in pyrite concentrates rather than it in pyrite tailings was observed at both pH 9 and 10.5 when pyrite was pre-conditioned in Ca/Mg-bearing solutions for 360 min. Fourier transform infrared (FTIR) spectroscopy showed the main xanthate derivatives changed from di-xanthogen (1155 cm-1 ) to FHX (1167 cm-1 ) on the oxidised pyrite samples that were preconditioned in Ca/Mg-bearing solutions. Scanning electron microscopy-energy dispersive spectrometry (SEM-EDS) suggested the preferential accumulation of FHX upon secondary Ca/Mg-bearing precipitates as reflected by the higher Fe/S ratio together with the decrease of O element herein after xanthate conditioning. Although the hydrophilic secondary Ca/Mg/Fe-bearing minerals on the pyrite surface generally deteriorate pyrite’s floatability, the upper section of these secondary hydrophilic aggregates is partially covered by FHX alongside with further multilayer-adsorbed di-xanthogen. The precipitated Ca/Mg-bearing precipitates promotes the immobilisation of dissociated FHX derived from the reaction among iron oxyhydroxides and xanthate anions upon the localised secondary Ca/Mg/Fe-bearing minerals via acid–base complexation. Therefore, this phenomenon alleviates the hydrophilic modification of secondary Ca/Mg/Fe-bearing minerals to pyrite considering the immobilised FHX upon localised precipitates shows a slight hydrophobicity, and meanwhile, the upper FHX benefits the multilayer adsorption of di-xanthogen via the interaction among their inner hydrophobic alkyl chains.