Ion irradiation, combined with nanoindentation, has long been recognized as an effective way to study effects of irradiation on the mechanical properties of metallic materials. In this research, hardening and creep of ion irradiated Chinese low activation martensitic (CLAM) steel are investigated by nanoindentation. Firstly, it is demonstrated that ion irradiation results in the increase of hardness, because irradiation-induced defects impede the glide of dislocations. Secondly, the unirradiated CLAM steel shows indentation creep size effect (ICSE) that the indentation creep strain decreases with the applied load, and ICSE is found to be associated with the variations of geometrical necessary dislocations (GNDs) density. However, ion irradiation results in the alleviation of ICSE due to the irradiation hardening. Thirdly, ion irradiation accelerates nanoindentation creep due to the large numbers of irradiation-induced vacancies whose diffusion controls creep deformation. Meanwhile, owing to the annihilation of vacancies, ion irradiation has a significant influence on the primary creep while only negligible influence has been observed for the steady-state creep.