In this study, the effect of extracellular metabolites produced by Saccharomyces cerevisiae on intracellular protein expression of Non-Saccharomyces cerevisiae and on the quality of wine was investigated by dialysis tube fermentation method. By using dialysis tubes with molecular weight cut-off value of 10.0 kD and 3.5 kD respectively in the mixed fermentation, the survival time of non- S. cerevisiae was extended to 18 days and 22 days correspondingly. Consequently the survival time of non-S. cerevisiae can be changed by limiting the exchange of metabolites between strains. 65 proteins, namely 13% of the total protein, were found differently expressed, with mass spectrometry results in-dicating their close relation to the biosynthesis of steroids, lysine, organic acids and ATP. Compared with 10.0 kD dialysis tube fermentation, in 3.5 kD dialysis tube, the concentration of tartaric acid in-creased by 5.1% while acetic acid decreased by 44.3%, which indicates that by allowing communication of metabolism between cells with limited molecular weight, we can adjust the yield of wine’s titratable acidity and volatile acidity.