Zirconium-based metal–organic framework UiO-66 catalyzes oxidation of propylene glycol (PG) using hydrogen peroxide as green oxidant. Hydroxyacetone (HA) is the main oxidation product, while the main side product is acetic acid (AcA). The nature of the solvent drastically affects PG adsorption, oxidant utilization efficiency and product yields. The best catalytic performance (85% selectivity towards HA at ca. 10% PG conversion) was achieved with water–acetonitrile (3/7 (v/v)) mixture as a solvent. Additives of radical chain scavengers produce a rate-inhibiting effect, suggesting radical chain mechanism of the oxidation process. The PG oxidation over UiO-66 proceeds without leaching of the active metal into solution, and the catalysis has a truly heterogeneous nature. The catalyst can be recycled without significant loss of activity and selectivity and retains its structure during at least five reuses.