High-resolution photoemission and density functional calculations on realistic slab surface models were used to study the interaction and subsequent dissociation of O-2 with Au nanoparlicles supported on TiC(001). The photoemission results indicate that at 150 K O-2 adsorbs molecularly on the supported gold nanoparticles, and upon heating to temperatures above 200 K the O-2 -> 2O reaction takes place with migration of atomic oxygen to the TiC(001) substrate. The addition of Au to TiC(001) substantially enhances the rate of O-2 dissociation at room temperature. The reactivity of Au nanoparticles supported on TiC(001) toward O-2 dissociation is much larger than that of similar nanoparticles supported either on TiO2(110) or MgO(001) surfaces, where the cleavage of O-O bonds is very difficult. Density functional calculations carried out on large supercells show that the contact of Au with TiC(001) is essential for charge polarization and an enhancement in the chemical activity of Au. Small two-dimensional particles which expose Au atoms in contact with TiC(001) are the most reactive. While O-2 prefers binding to Au sites, the O atoms interact more strongly with the TiC(001) surface. The oxygen species active during the low-temperature (<200 K) oxidation of carbon monoxide on Au/TiC(001) is chemisorbed O-2. Once atomic O binds to TiC(001), the chemisorption bond is so strong that temperatures well above 400 K are necessary to remove the O adatoms from the TiC(001) substrate by direct reaction with CO. The high reactivity of Au/TiC(001) toward O-2 at low-temperature opens the route for the transformation of alcohols and amines on the supported Au nanoparticles.