Ni-based catalysts derived from Ni-Mg/Al ternary hydrotalcites with low Ni-loadings have been prepared for the partial oxidation of methane (POM) to syngas. The reducibility, surface basicity, and effects of catalyst reduction on POM reactivity over these catalysts have been explored. Temperature-programmed reduction and CO2-temperature-programmed desorption results indicate that the amount of Ni-loading and the Mg/Al molar ratio exert a remarkable influence on their reducibility but have little influence on the surface basicity, with an increase in Mg/Al ratio also lessening the base strength of the alkaline sites. Reaction temperature significantly affects the reactivity of the catalysts, and high temperature reduction of the catalysts can lead to superior reactivity to those reduced at low temperature. An in situ reduction of the catalyst has been observed in the POM reaction for catalysts reduced at low temperature. Under the optimized reaction conditions, the catalysts with Ni content from 8 wt % to 15.5 wt % show similar activity in POM reactions, and this activity is much higher than for catalysts with lower Ni-loading (similar to 4 wt %), which is explained in terms of nickel reducibility and the surface basicity of the catalysts.