This study aimed to optimize through design of experiments, the process variables (temperature - T, time - t and solid-to-liquid ratio - SLR) for sugarcane bagasse (SB) autohydrolysis (AH) to obtain hemicellulose hydrolyzates (HH) prone to anaerobic digestion (AD) and biochemical methane production (BMP). The results indicated that severe AH conditions, which lead to maximum hemicelluloses dissolution and sugar content in the HH, were not the best for BMP, probably due to the accumulation of toxic/recalcitrant compounds (furans and lignin). Mild AH conditions (170 degrees C, 35 min and SLR = 0.33) led to the highest BMP (0.79 Nm(3) kg TOC (1)), which was confirmed by the desirability tool. HH produced by AH carried out at the desired condition DC2 (178.6 degrees C, 43.6 min and SLR = 0.24) showed the lowest accumulation of inhibitory compounds and volatile fatty acids (VFA) and highest BMP (1.56 Nm(3) kg TOC (1)). The modified Gompertz model best fit the experimental data and led to a maximum methane production rate (R) of 2.6 mmol CH4 d (1) in the best condition. (C) 2015 Elsevier Ltd. All rights reserved.