The basic oxygen furnace slag (SL) was selectively leached by NH4Cl. Response surface methodology and the central composite design (CCD) were employed in determining the optimal condition. The process parameters such as leaching duration, NH4Cl concentration, liquid solid ratio (LSR), and leaching temperature were chosen as independent variables in CCD. The quadratic model was developed for process optimization and statistical experimental designs. It is found that the leaching duration, NH4Cl concentration and liquid solid ratio are significant to the extraction of Ca2+ and Mg2+. The optimal conditions with setting maximum extraction of calcium and magnesium cations from SL are as following: 68 min (X1), 1.8 mol/L NH4Cl (X2), LSR 12 mL/g (X3), 53°C (X4), with the predicted Ca2+ and Mg2+ concentration reaching 13.3 and 3.2 g/L, respectively. The proposed simplified leaching mechanism indicates a two‐stage leaching. The prone leachable MgFe2O4 and Ca2Fe2O5 are extracted in the fast stage, while the extraction of CaO occurs throughout slow stage. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 1387–1394, 2016