Autothermal reforming (ATR) is an effective route for hydrogen production from acetic acid (HAc) derived from biomass. Ni-based catalysts are promising candidates for ATR due to their high activity, but coke formation hinders their practical application. To tackle this issue, a series of Ni-Mg-Cr catalysts with supports of Cr 2 O 3 or MgCr 2 O 4 were prepared by the sol−gel method and evaluated in ATR. The results indicated that as compared to the Ni-Cr 2 O 3 catalyst, the Ni 0.25 Mg 0.75 CrO 3.5±δ catalyst with MgCr 2 O 4 support presented higher catalytic performance: the conversion rate of acetic acid was stable near 100%, with hydrogen yield reaching 2.64 mol-H 2 /mol-HAc during a 40 h ATR test, while there was no obvious coking. It was found that Mg modification was prone to constituting a stable MgCr 2 O 4 spinel support with a high specific surface area for adsorption and transformation of HAc; however, for catalysts with excessive Mg addition, namely, Ni 0.43 Mg 2.56 CrO 4.5±δ and Ni 0.69 Mg 5.31 CrO 7.5±δ , low reactivity was found and was linked to constraining of Ni from the solid solution of Mg(Ni)O. Density functional theory (DFT) calculations reveal that during the ATR process, Ni 4 -MgCr 2 O 4 presents a low energy barrier for the overall transformation path and a high stabilization of reaction intermediates; furthermore, as compared to Ni 4 -Cr 2 O 3 , oxidation of C* species by O* and OH* is significantly accelerated on Ni 4 -MgCr 2 O 4 due to the considerably decreased energy barriers, thus eliminating carbon deposition and improving catalytic activity.