The toxic level of acetic acid could be released during the pretreatment of lignocellulosic biomass, and an economical method was reported to minimize the acidic stress on the fermentation of Saccharomyces cerevisiae by cation supplementation. A dose-dependent protection of Ca2+ was monitored, and the optimal concentration of Ca2+ was 8 mM under 4.5 g/L acetic acid stress. The activities of catalase and superoxide dismutase of yeast cells supplemented with optimal Ca2+ increased by 18.6 and 27.3 %, respectively, coupling with an obvious decrease of reactive oxygen species content. Cell viability also performed a significant increase from 52.4 % (without Ca2+ addition) to 73.56 % (with 8 mM Ca2+ addition). No significant improvements were found in the bioethanol yields by Ca2+ supplementation; however, the fermentation time was shortened by about 8 h obviously. Our results illustrated that the Ca2+ supplementation could be an economical method to make the bioethanol production more efficient and cost-effective.