To investigate the application of iron tailings in cement-based materials as fine aggregate and mineral admixture, six iron tailings sands were selected from different places of origin, and the methods of acid and alkali activation were adopted to increase the activity of tailings powder. The strength of mortar was evaluated and the composition and microstructure were analyzed to explore the mechanism. The experimental results show that iron tailings sands had little adverse effect on the mortar strength, and there was a maximum increase of 13.2% in 28-day compressive strength compared with that of river sand mortar. The hardness values of all the iron tailings sand and the interfacial transition zone (ITZ) around them were higher than that of natural river sand, but their Ca/Si ratios in the ITZ was lower, indicating a chemical reaction occurred between the iron tailings and cement paste. Generally, the iron tailings sand with higher SiO₂ content and finer particles tend to have higher activity. In addition, the pozzolanic activity of iron tailings powder could be greatly promoted by chemical activation, especially by acid activation. The activity index of cement mortar with unactivated iron tailings powder was only 63% at 28 days, whereas that of acid-activated and compound-activated samples reached up to 93%, and the heights of the maximum heat flow peak of these samples were even higher than that of the control sample without iron tailings powder, and the time to reach the peak was in some advance, moreover their impedance parameters were close to the control sample.