This study was prompted by the phenomenon of the optimal conditions for nickel and copper extractions were quite different in the bioleaching of a low grade complex nickel-copper concentrate. Response surface methodology (RSM) was firstly utilized to promote chalcopyrite oxidation under optimal condition of nickel recovery. The experiment results showed that a satisfactory second-order polynomial regression equation was achieved with a high coefficient of determination (R²=0.9522) which demonstrated that the model could be effectively applied for optimization of silver-catalyzed bioleaching process. Based on the model, the term of silver-bearing species and the interaction term of adding time and Ag⁺ concentration exhibited high contribution to copper extraction. The different effect of silver-bearing species on bioleaching was revealed by RSM. Besides, the addition time of silver was quite significant in silver-catalyzed bioleaching process, which has never been reported. The high copper extraction reached 0.814 under the optimal conditions of Ag₂SO₄ as silver-bearing species, adding catalyst after 7 d of bioleaching and Ag⁺ concentration 1.1 g Ag/kg of ore. Moreover, validation tests were performed and the results were very close to the predicted values.