Helium is produced in spent nuclear fuel by α-decays of actinides. After 10,000 years, the concentration of He accumulated in UO2 spent fuel is about 0.23 at.%. For direct disposal of spent nuclear fuel, consequences of helium build-up on the fuel matrix microstructure must be evaluated since it can modify the radionuclide release when water comes into contact with the spent fuel surface, after breaching of the disposal canister. An operational model has been proposed in order to evaluate the effect of helium on the microstructure of spent fuel in a repository. Based on conservative assumptions and different scenarios of bubble population, the calculated helium critical concentration, that could lead to a partial loss of integrity of the spent fuel pellet, is 0.37 at.%. However, observations on He-implanted UO2, α-doped UO2 pellets and natural analogues evidence a macroscopic damage only for He concentrations, which are more than one order of magnitude higher.