The recalcitrant structures of sugarcane straw and related lignocellulosic biomasses require a pretreatment step to enable a better enzymatic attack during the hydrolysis. Factors like the energy consumption and the formation of inhibitors require the optimization of the pretreatment step. Thus, the influence of different severity factors (SF) on hydrothermal (also called liquid hot water, LHW) pretreatment was evaluated using a factorial design 22 with central point. The obtained results showed that low values of SF (< 3.39) did not promote reasonable alteration in the sugarcane straw structures, whereas high SF values (> 4.70) resulted in loss of hydrolyzed sugars, generation of inhibitors such as furfural, and formation of pseudo-lignin structures, despite high hemicellulose removal (similar to 97%). The residence time exhibited low influence on LHW. An optimum condition was found for the process (10 min and 195 degrees C) with low cellulose solubilization (9.80%) and a reasonable hemicellulose removal (85.45%).