Abstract: With the breakthrough of cellulose pretreatment and enzyme hydrolysis technology, fermentation has become one of the main limiting factors for process enhancement. Current fermentation techniques are still dominated by the old-fashioned batch mode production with the lag and stationary phase demanding considerable operational time. This handicaps production efficiency and economic viability. In addition, a downtime between two batches is requested for harvesting, cleaning and sterilization, which reduces the overall productivity and increases human labor. Continuous culturing in chemostat, on the other hand, can enhance production and reduce labor (e.g. eliminating downtime intervals, and prior-fermentation steps like shake-flask culture, inoculation and subculture). However, ethanol content might be diluted, making downstream distillation and purification difficult and costly. This study endeavors to explore possible unsteady-state operation/control strategies to improve process performance. Starting from a simplified model of ethanol fermentation, stability analysis of the semi-continuous fermentation process is performed and the instability conditions of the system under ethanol inhibition is conducted. Based on the optimal periodic control (OPC) theory, the optimal criteria for switch production by periodic operations are explored, and the benefit of periodic dilution rate in the chemostat model in terms of averaged conversion rate is discussed. The results show that for the classical chemostat model with a Monod growth function, the performance of the averaged conversion rate can be improved under certain conditions, thus providing theoretical support for the study of self-cyclic fermentation.