Since the formation of helium bubbles degrades swelling property and thermal conductivity of minor actinide-containing mixed oxide (MA-MOX) fuel, it is essential to understand the conditions of the bubble formation. In order to examine the dependence of vacancy concentration on morphology of helium bubbles, helium was infused into (Zr,Fe)O 2−x . The oxygen vacancy concentration was controlled by addition of solute Fe 3 + into ZrO 2 . Helium was infused by hot isostatic pressing. The helium-infused specimens were observed by field emission scanning electron microscopy (FE-SEM) and field emission transmission electron microscopy (FE-TEM). In addition, X-ray fluorescence, X-ray diffraction analysis, conversion electron yield-X-ray absorption near-edge structure and FE-SEM/EDX (energy dispersive X-ray) analyses were also made to interpret the results of microstructure observations. As a result of the helium infusion treatment, numerous 0.5-10 nm bubbles were observed and its number density clearly depended on oxygen vacancy concentration. On the other hand, sizes of the helium nano-bubbles in all specimens were almost constant.