A mesophilic co-digestion of sugarcane straw and sewage sludge with long-hydraulic retention time in lab-scale reactors has been studied. The both design of the experiment method and the I-optimal mixture design were used as a mixed design strategy to systematically optimization of the substrate composition ratios and elucidate the possible synergistic effects for an anaerobic co-digestion system. A reduced cubic model was created by Design-Expert software as a function of substrate composition ratios. The model was experimentally validated by ANOVA. Based on the observations, all linear impacts and interactions between substrates showed synergistic effects on the biogas production rate. The optimum proportions of the feedstock were 0.28% (w/w) of Primary sludge (A), 48.98% (w/w) of Secondary sludge (B), and 50.73 % (w/w) of sugarcane straw (C). According to the aforementioned optimum proportions, the amount of cumulative biogas reaches the maximum level of 8581 mL during 150 days.
