Abstract:[Background] The application of commercial yeasts has caused a serious problem of wine homogenization. It is significant to explore excellent indigenous strains of Saccharomyces cerevisiae. [Objective] To screen out the S. cerevisiae strains with excellent wine fermentation performance from 168 yeast strains isolated from the eastern foothills of Helan Mountains. [Methods] Duchenne tube fermentation, tolerance tests, and H2S production experiments and growth curve establishment were employed to screen out the indigenous S. cerevisiae strains with excellent fermentation ability, strong stress tolerance, and low H2S production for Cabernet Sauvignon wine production. We determined the basic physicochemical indexes and the content of phenols and volatile compounds in wine samples to explore the fermentation characteristics of the candidate yeast strains. [Results] Four indigenous S. cerevisiae strains, YC-E8, QTX-D17, QTX-D7, and YQY-E18 with rapid fermentation, low H2S production, and tolerance to 13% ethanol, 350 g/L glucose, 250 mg/L SO2, and pH 1.0 were preliminarily screened out. The strain YC-E8 showed high glycerol production and produced the wine sample with similar aroma to those prepared with commercial yeasts XR and F33, being suitable for brewing Cabernet Sauvignon wine. The wine sample fermented with strain QTX-D17 had the highest content of alcohol, tannin, total phenols, and anthocyanins, which indicated the excellent fermentation characteristics of QTX-D17. In the wine sample fermented with strain QTX-D7, the content of ethyl acetate, ethyl caprylate, and 1-nonanol endowing the wine with pleasant floral and fruity aromas such as banana, apple, pineapple, and coconut aromas were higher. [Conclusion] Finally, three indigenous S. cerevisiae strains QTX-D17, YC-E8, and QTX-D7 were screened out. The three strains exhibit diverse fermentation characteristics in the winemaking process and provide novel yeast strains for exploiting the microorganism resources in the wine-producing region at the eastern foothills of Helan Mountains in Ningxia.