Lignocellulosic biomass is a promising bioprocess substrate for the production of biofuels and biomaterials. This study modeled and optimized the production of xylose and glucose from sugarcane leaves subjected to hybrid pretreatment of HCl and moist heat and, it examined the dynamics of hydrogen biofuel production from these substrates at a semi pilot scale. The response surface methodology was used to optimize the hybrid pretreatment within the ranges of 4-10%, 60-100 degrees C and 60-240 min for HCl concentration, temperature and process time respectively. The coefficients of determination (R-2) of 0.99 and 0.93 were obtained for xylose and glucose models respectively indicating the suitability of the models to navigate the optimization space. Process optimization predicted Xylose and glucose yields of 8.92 g/l and 1.68 g/l on a hybrid pretreatment of 5.28% HCl for 187 min at 94.94 degrees C. Experimental validation yielded xylose and glucose of 8.6 g/l and 1.78 g/l. Biohydrogen production on these optimized substrates in 13L bioreactor showed a peak hydrogen fraction of 26.73% at the 30th hour, and hydrogen yield of 248.05 ml H-2 g(-1) of fermentable sugar. These findings demonstrate that sugarcane leaves which are usually burnt during harvesting can be an excellent renewable source of fermentable sugars for the production of biofuels such as hydrogen. Copyright (C) 2015, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.