Uranium hexafluoride, or UF₆, is a compound used in the uranium enrichment process that produces fuel for nuclear reactors and nuclear weapons. It forms solid grey crystals at standard temperature and pressure (STP), is highly toxic, reacts violently with water and is corrosive to most metals. It reacts mildly with aluminum, forming a thin surface layer of Al₂F₃ that resists further reaction.

Milled uranium ore -- U₃O₈, or "yellowcake" -- is dissolved in nitric acid, yielding a solution of uranyl nitrate UO₂(NO₃)₂. Pure uranyl nitrate is obtained by solvent extraction , then treated with ammonia to produce ammonium diuranate (ADU ). Reduction with hydrogen gives UO₂, which is converted with hydrofluoric acid (HF) to UF₄. Oxidation with fluorine finally yields UF₆.

It is used in both of the main uranium enrichment methods: gaseous diffusion and the gas centrifuge method because of the following properties:

• a triple point at 64 °C (147 °F) and slightly higher than normal atmospheric pressure
• fluorine has only a single stable naturally occurring isotope, so isotopes of UF₆ differ in their molecular weight based solely on the uranium isotope present.

Gaseous diffusion costs ca. 60 times as much energy as the gas centrifuge; even so, this is just 4% of the energy that can be produced by the resulting enriched uranium.