Pyrite, as a disturbing gangue mineral in the beneficiation of valuable sulfide minerals and coal resources, is usually required to be depressed for floating in flotation practice. Specifically, the depression of pyrite is achieved by causing its surface to be hydrophilic with the assistance of depressants, normally with inexpensive lime used. Accordingly, the progressive hydrophilic processes of the pyrite surface in high-alkaline lime systems were studied in detail using density functional theory (DFT) calculations in this work. The calculation results suggested that the pyrite surface is prone to hydroxylation in the high-alkaline lime system, and the hydroxylation behavior of the pyrite surface is beneficial to the adsorption of monohydroxy calcium species in thermodynamics. Adsorbed monohydroxy calcium on the hydroxylated pyrite surface can further adsorb water molecules. Meanwhile, the adsorbed water molecules form a complex hydrogen-bonding network structure with each other and with the hydroxylated pyrite surface, which makes the pyrite surface further hydrophilic. Eventually, with the adsorption of water molecules, the adsorbed calcium (Ca) cation on the hydroxylated pyrite surface will complete its coordination shell surrounded by six ligand oxygens, which leads to the formation of a hydrophilic hydrated calcium film on the pyrite surface, thus achieving the hydrophilization of pyrite.