NiO catalysts supported on MgAl2O4 spinel were prepared by ball-milling method, and the effects of Ni source, NiO loading, ball-to-powder ratio, ball-milling speed and calcination temperature on catalytic lean burn of high-diluted methane were investigated with instruments like H2-TPR, BET, XRD and SEM, etc. Weaker interaction between the Ni precursor and carrier was found in catalysts prepared by ball-milling than by impregnation or deposition-precipitation, to produce the NiO species with higher catalytic activity after calcination. In ball milling, the factors of Ni source and loading, ball-to-powder ratio and ball-milling speed, and calcination temperature as well, all can affect catalytic performance by altering the grain size or bonding state of NiO species on carrier surface. The NiO/MgAl2O4 catalyst prepared from nickel acetate with 10% in mass fraction of NiO loading, ball-milled at ball-to-powder ratio of 2∶1 and 400 r/min, and calcined at 700℃ has demonstrated better stability and activity, and its pseudo first-order reaction rate constant at 600℃ was 0.489 L/(g·s), which is higher than that of La0.8Ca0.2FeO3 or La0.8Sr0.2MnO3 perovskite supported on MgAl2O4 spinel.