For mines located in saline areas, the use of mine water containing chloride salts to prepare cemented tailings backfill (CTB) for mined-out area treatment can realize the resource utilization of mine water and save a large amount of precious freshwater. However, the hydration behavior of binder and strength properties of CTB in the presence of chloride salts is still not well understood. This research investigates the effects of NaCl, CaCl2 and MgCl2 with different Cl- concentrations (0.50, 0.77 and 1.0 mol/L) on strength of CTB prepared with one-part alkali-activated slag binder. It analyzes the hydration process of binder and the microstructure of CTB. The results indicated that the decalcification of C-A-S-H (replaced by sodium to create N(C)-A-S-H at high Na+ concentrations) leads to numerous 0.01–0.1 μm micropores within the hardened backfill, increasing porosity while decreasing strength by 3.2–25.0%. Calcium ion (Ca2+) contributes to the formation of dense internal structures and high-strength backfill. Magnesium ion (Mg2+) reduces alkalinity by consuming Ca(OH)2, seriously impacts slag decomposition, but accelerates the dissolution of desulfurized gypsum. The study’s findings will help the application of chloride-containing mixing water in mines situated in saline regions.