This study reports a hybrid pretreatment strategy for optimum fermentable sugar (FS) release from cassava peels waste. The Response Surface design method was used to investigate the effect of soaking temperature, soaking duration, autoclave duration, acid concentration and solid loading on reducing sugar yield. The model gave a coefficient of determination (R-2) of 0.87. The optimum pretreatment conditions of 69.62 degrees C soaking temperature, 2.57 h soaking duration, 5 min autoclave duration, 3.68 v/v acid concentration and 9.65% w/v solid loading were obtained. Maximum reducing sugar of 89.80 +/- 2.87 g/L corresponding to a fermentable sugar yield of 0.93 +/- 0.03 g/g cassava peels was achieved Upon model validation. A percentage sugar recovery of 90.79% was achieved with a 31% improvement in the FS yield from the enzyme pretreatment. The combined severity factor (CSF) of 0.77 and the low concentration of inhibitory compounds achieved further demonstrates the efficiency of this technique.