Nano-oxides are largely responsible for the excellent mechanical properties and irradiation tolerance of nano-structured ferritic alloys (NFAs) for nuclear reactor applications. In this work, the roles of perovskite YTiO3 and its interface in trapping helium in NFAs were investigated from the first-principles. Similarly as other two Y-Ti-oxide phases (Y2TiO5 and Y2Ti2O7), bulk YTiO3 can trap insoluble helium at its interstitial sites, but with a lower trapping ability that is only comparable to matrix vacancies. The ferrite/YTiO3 interface phase diagram was constructed based on the experimental orientation relationship and the calculated interface formation energy, and the lowest-energy interface structure was predicted as the ns-Ti or the stoichiometric. Helium always prefers to consume individual interfacial vacancies and interstitial sites to the extent possible, before forming higher-order helium-vacancy clusters at the interface. Similarly as Y2Ti2O7, YTiO3 preferably traps helium at its interface, followed by its bulk interior and the ferritic matrix. However, in view of all the bulk and interface results, perovskite YTiO3 cannot compete with pyrochlore Y2Ti2O7 in trapping helium in NFAs.