V–4Cr–xTi (x = 0 to 4) alloys were used to investigate the additional effect of Cr, Ti and interstitial impurities on the microstructural evolution in He-irradiated V–Cr–Ti alloys to minimize radioactivity after fusion neutron irradiation. Transmission electron microscopy and atom probe tomography were carried out to the He-irradiated specimens at 500 °C with 0.5 dpa at peak damage. A flash electro-polishing method for the FIB-extracted specimen was established for the ion-irradiated vanadium alloys. The microstructural evolution of the irradiation-induced titanium-oxycarbonitride, Ti(CON) precipitates was observed and was influenced by the effect of Ti addition on the Ti(CON) precipitation. Apparent Ti(CON) precipitates formed in V-4Cr-xTi with 2% addition of Ti. In the V-4Cr-1Ti alloy, a high density Ti enriched cluster was formed. The origin of the irradiation hardening increase resulted from the size distribution of Ti(CON) precipitation from the dispersed barrier-hardening theory.