The effects of oxygen pick-up in an irradiation environment in a vacuum chamber during ion-and neutronirradiation of V-4Cr-4Ti alloys were studied. The density and size of titanium oxides in the alloys were found to drastically increase because of the oxygen pick-up, especially for cases of higher irradiation dose and specimen temperature. Using Zr foil as a diffusion barrier and doping the V-4Cr-4Ti alloys with Y can be considered as effective techniques for reducing the reaction of Ti with C, O, and N to form Ti(C,O,N) because of oxygen-pick up from irradiation environment.