The effect of O6+ion irradiation on the microstructure of pre-deformed V-4Cr-4Ti alloy has been reported in this study. Changes in the microstructure has been assessed using detail X-ray diffraction line profile analysis in terms of the coherent domain size, rms micro-strain, dislocation density, their nature and their arrangement etc., revealing the importance of pre-deformation in controlling the material response to irradiation. The results are supported by Electron back scattered diffraction and Transmission electron microscopy. Energy Dispersive X-ray analysis has been used to map the micro-chemical changes caused in the sample due to the ion irradiation. Vicker’s micro-hardness values were determined to understand the effect of irradiation on the mechanical property of the alloy. The results are explained in terms of the occurrence of vacancy-solute complexes, the formation of which isestablished using Density Functional Theory calculations..