This work presents a quantitative predicting likely acid mine drainage (AMD) generation process throughout tailing particles resulting from the Sarcheshmeh copper mine in the south of Iran. Indeed, four predictive relationships for the remaining pyrite fraction, remaining chalcopyrite fraction, sulfate concentration, and pH have been suggested by applying the gene expression programming (GEP) algorithms. For this, after gathering an appropriate database, some of the most significant parameters such as the tailing particle depths, initial remaining pyrite and chalcopyrite fractions, and concentrations of bicarbonate, nitrite, nitrate, and chloride are considered as the input data. Then 30% of the data is chosen as the training data randomly, while the validation data is included in 70% of the dataset. Subsequently, the relationships are proposed using GEP. The high values of correlation coefficients (0.92, 0.91, 0.86, and 0.89) as well as the low values of RMS errors (0.140, 0.014, 150.301, and 0.543) for the remaining pyrite fraction, remaining chalcopyrite fraction, sulfate concentration, and pH prove that these relationships can be successfully validated. The results obtained also reveal that GEP can be applied as a new-fangled method in order to predict the AMD generation process.