In this study, zero-valent iron (ZVI) is applied to activate persulfate (PDS) for the degradation of amaranth (AMR). The effects of PDS concentration, ZVI concentration, solution pH , temperature, and reaction time on the degradation of AMR by the ZVI/PDS advance oxidation process are investigated. Sulfate and hydroxyl radicals are involved in the main reaction pathway of AMR and sulfate radical acts as a dominant oxidant. The CCD (central composite design) plan is chosen to build the RSM model for the prediction of AMR degradation. ANOVA analysis shows that the secondary fitting model had great fitness with R2 = 0.997, $$R_{{{\text{adj}}}}^{2}$$
R
adj
2
= 0.936, p-value of lack of fit = 0.107. Optimum conditions for 98% AMR removal given by RSM are PDS concentration = 7.33 mM, ZVI dosage = 17.79 mM, initial pH 4.62, temperature = 59.49 °C, reaction time = 9.88 min which is proved to be very closed to the real removal rate of 96.78%. Sensitivity analysis indicates that the relative importance of the influencing parameters is of the following order: temperature, PDS concentration, pH , ZVI dosage, and reaction time. The PDS/ZVI system shows an acceptable RSE of about 75% and TOC removal of 85% on AMR oxidation. Finally, the possible pathway of AMR degradation is proposed.