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Utilizing iron tailings powder (ITP) as supplementary cementitious materials (SCMs) has significant economic and environmental benefits, while the low pozzolanic activity of ITP limits its incorporation to some extent. This paper aims to study the effect of compound activation (wet grinding with a chemical activator) on the activity of ITP. Two kinds of sulfate (CaSO4·2H2O and Na2SO4) were used as chemical activators, and the optimal dosages of CaSO4·2H2O and Na2SO4 were determined by the mechanical strength tests of cement-ITP pastes. Results demonstrate that adding 3 % CaSO4·2H2O (wet grinding with ITP) caused a slight increase in the early and later strength of cement pastes containing 30 % ITP, while adding 3 % Na2SO4 (wet grinding with ITP) resulted in a significant improvement in the early strength and a slight increase in the later strength. Compared to a single wet grinding activation, compound activation could produce more amorphous substances in ITP and cause a more prominent decrease in the surface binding energy of internal chemical bonds of ITP, thereby further improving the activity of ITP. Moreover, the hydration products of cement pastes containing 30 % compound activated ITP were compared with those of cement pastes containing 30 % wet ground ITP, and the activation mechanism of two sulfates on ITP was studied.