In enzymology, a 4-hydroxymandelate oxidase (EC 1.1.3.19) is an enzyme that catalyzes the chemical reaction

(S)-2-hydroxy-2-(4-hydroxyphenyl)acetate + O₂ ${\displaystyle \rightleftharpoons }$ 4-hydroxybenzaldehyde + CO₂ + H₂O₂

Thus, the two substrates of this enzyme are (S)-2-hydroxy-2-(4-hydroxyphenyl)acetate and O₂, whereas its 3 products are 4-hydroxybenzaldehyde, CO₂, and H₂O₂.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with oxygen as acceptor. The systematic name of this enzyme class is (S)-2-hydroxy-2-(4-hydroxyphenyl)acetate:oxygen 1-oxidoreductase. This enzyme is also called L-4-hydroxymandelate oxidase (decarboxylating). It has 2 cofactors: FAD, and Manganese.