The x%Ni/Sm2O3-MnO (x = 0, 10, 15, 20) catalysts derived from SmMn2O5 mullite were prepared by solution combustion and impregnation method; auto-thermal reforming (ATR) of acetic acid (HAc) for hydrogen production was used to explore the metal-support effect induced by Ni loadings on the catalytic reforming activity and product distribution. The 15%Ni/Sm2O3-MnO catalyst exhibited optimal catalytic performance, which can be due to the appropriate Ni loading inducing a strong metal-support interaction to form a stable Ni/Sm2O3-MnO active center, while side reactions, such as methanation and ketonization, were well suppressed. According to characterizations, Sm2O3-MnO mixed oxides derived from SmMn2O5 mullite were formed with oxygen vacancies; nevertheless, loading of Ni metal further promoted the formation of oxygen vacancies, thus enhancing adsorption and activation of oxygen-containing intermediate species and resulting in higher reactivity with HAc conversion near 100% and hydrogen yield at 2.62 mol-H2/mol-HAc.