“…Due to its excellent abilities such as handling data with high dimensionality, the approximation for arbitrary nonlinear functions, and computational efficiency, the artificial neural network (ANN) system has successfully provided a good representation in biological, chemical, and physical phenomena . Recently, the advanced system that aims to balance the compromise between the accuracy of models and cost‐effectiveness of collecting limited numbers of experimental conditions, of which combines both advantages of ANNs and the response surface methodology (RSM), has been reported . Although many works have been done using the RSM as a tool for the optimization of hydrogen dark fermentation, the employment of the hybrid ANNs‐RSM system and its application in the investigation of the effect of critical operational conditions, ie, BC, metal cofactor Ni 0 , pH, and dosage of microbes upon hydrogen production, to the best of our knowledge, have never been reported before.…”