<P>The high cost of the lignocellulose-degrading enzyme is one of the major bottlenecks for economically producing cellulosic ethanol. To overcome this bottleneck, we performed <I>in</I>-<I>situ</I> vacuum distillation (at 50 °C, 77 mmHg for 30 min) to remove ethanol after simultaneous saccharification and fermentation (SSF) of delignified corncob residues (DCCR). The cellulase and yeast cells left in the stillage were reused by adding fresh DCCR to start a new cycle. This process cycle was repeated five times. Both cellulase and yeast cells were reused five times with a significant cellulase reduction from 16.3 mg of enzyme protein (EP)/g cellulose to as low as 3.3 mg EP/g cellulose. Meanwhile the ethanol in the fermentation broth was maintained as high as 40 g/L before each vacuum distillation. The final ethanol yield after five cycles reached 72.7%. The process economic analysis based on the Aspen Plus model indicated that the cost of the saved cellulase was much higher than that of the additional energy needed to carry out the vacuum distillation. Almost 24% of the ethanol production cost could be reduced by using this new approach compared to batch SSF without cellulase recycling.</P><P>Cellulase and yeast were recycled five times via <I>in</I>-<I>situ</I> vacuum distillation during SSF, and 24% of ethanol production cost was saved.</P><P><B>Graphic Abstract</B><BR><IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ascecg/2017/ascecg.2017.5.issue-12/acssuschemeng.7b03084/production/images/medium/sc-2017-030848_0006.gif'></P>