The global need for the production of biofuels, has led to explore new strategies process and use alternative raw materials in order to optimize production, for this reason this research is developed in the study of the ethanol production process from flour cassava integrating the stages of enzyme hydrolysis (liquefaction and saccharification) and fermentation simultaneously (HEFS), using the enzyme complex Stargen TM 001. The experimental design was a response surface central composite design with two factors and two levels (temperature: 48 - 80 ° C and agitation: 400 - 600 rpm) in liquefaction stages previous, and then the temperature was adjusted to 37 ° C keeping the other conditions in the integration process of the stages. The experimentation was developed with a solids concentration of cassava flour of 28% w/v, pH 5.3, inoculums of 0.75 g/l of yeast Ethanol Red ®, and an enzyme concentration of 4 ml / l. The temperature is variable with greatest effect on the production of ethanol when compared to the agitation, though; both factors have statistic significance on the response variable. A 64 ° C and 500 rpm is reached an ethanol concentration of 14.6% v/v and a productivity of 2.5 g/lh (at 48 hours of processing)