This study focused on the development of an efficient technology for bioconversion of cassava to bioethanol without high temperature digesting. Mechanical activation (MA, ball milling)-metal salt (MA-MS) technology was applied to pretreat cassava flour, leading to significant changes in crystal structure, morphology, and viscosity. The destruction of stable structure of cassava flour induced by MA-MS pre-treatment increased the accessibility of glucoamylase to starch granules from surface to interior, which contributed to direct and efficient saccharification of cassava flour without digesting. The decrease in viscosity of slurry and the use of metal salt as nutrient for yeast (Saccharomyces cerevisiae) had favorable effect on fermentation process. The combination of MA and MgSO4 exhibited outstanding synergistic interaction. The ethanol concentration and conversion efficiency of MA-MgSO4 pretreated cassava flour achieved 13.64 vol% and 93.4% under optimum conditions (addition amount of MgSO4 = 6 wt%, MA time = 75 min, dosage of glucoamylase = 200 U/g cassava, and dosage of Saccharomyces cerevisiae = 0.3 wt%). MA-MS pretreatment significantly enhanced the saccharification and fermentation processes for efficient bioconversion of cassava to bioethanol by non-digesting strategy. (C) 2021 Elsevier Ltd. All rights reserved.