[2][3] Hexafluorophosphate salts can be prepared by the reaction of phosphorus pentachloride and alkali or ammonium halide in a solution of hydrofluoric acid:[4] Hexafluorophosphoric acid can be prepared by direct reaction of hydrogen fluoride with phosphorus pentafluoride.

These reactions require specialized equipment to safely handle the hazards associated with hydrofluoric acid and hydrogen fluoride.

[10] Nonetheless, hexafluorophosphate is prone to decomposition with the release of hydrogen fluoride in ionic liquids.

One example is the synthesis of rhodocenium salts:[13] The overall conversion equation is Tetrakis(acetonitrile)copper(I) hexafluorophosphate is produced by the addition of hexafluorophosphoric acid to a suspension of copper(I) oxide in acetonitrile:[14] While the hexafluorophosphate ion is generally inert and hence a suitable counterion, its solvolysis can be induced by highly electrophilic metal centers.

[15][16] Practical uses of the hexafluorophosphate ion typically exploit one or more of the following properties: that it is a non-coordinating anion; that hexafluorophosphate compounds are typically soluble in organic solvents, particularly polar ones, but have low solubility in aqueous solution; or, that it has a high degree of stability, including resistance to both acidic and basic hydrolysis.

This salt, in combination with dimethyl carbonate, is a common electrolyte in commercial secondary batteries such as lithium-ion cells.