HMG-CoA reductase (or 3-hydroxy-3-methyl-glutaryl-CoA reductase or HMGR) is the rate controlling enzyme ( ) of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids. This enzyme is anchored in the membrane of the endoplasmic reticulum, and was long regarded as having seven transmembrane domains, with the active site located in a long carboxyl terminal domain in the cytosol. More recent evidence shows it to contain eight transmembrane domains .

The CAS number for this enzyme is [37250-24-1]; the enzyme commission designation is EC 1.1.1.34 for the NADPH dependent enzyme, whereas 1.1.1.88 links to an NADH dependent enzyme.

In humans, the gene for HMG-CoA reductase is located on the long arm of the fifth chromosome (5q13.3-14). Related enzymes having the same function are also present in other animals, plants and bacteria.