The potential of wastes obtained from the cultivation of Manihot esculenta Crantz as raw material for bioethanol production was studied. The objective was to determine the optimal conditions of hemicellulose thermohydrolysis of cassava stems and peelings and evaluate their impact on the enzymatic hydrolysis yield of cellulose. An experimental design was conducted to model the influence of factors on the pentose, reducing sugar and phenolic compound contents. Residues obtained from the optimal pretreatment conditions were hydrolysed with cellulase (filter paper activity 40 FPU/g). The hydrolysates from pretreatment and enzymatic hydrolysis were fermented respectively using Rhyzopus spp. and Sacharomyces cerevisiae. The yield of enzymatic hydrolysis obtained under the optimal conditions were respectively 73.1% and 86.6% for stems and peelings resulting in an increase of 39.84% and 55.40% respectively as compared to the non-treated substrates. The ethanol concentrations obtained after fermentation of enzymatic hydrolysates were 1.3 and 1.2 g/L respectively for the stem and peeling hydrolysates. The pentose and phenolic compound concentrations obtained from the multi-response optimization were 10.2 g/L; 0.8 g/L and 10.1 g/L; 1.3 g/L respectively for stems and peelings. The hydrolysates of stems and peelings under these optimal conditions respectively gave ethanol concentrations of 5.27 g/100 g for cassava stems and 2.6 g/100 g for cassava peelings. (C) 2016 Published by Elsevier Ltd.