n-Butanol is a chemical widely used in industry, with an approximate annual output of 4 million tons and a market valued at USD 8.6 billion. It was first produced by ABE fermentation (acetone - n-butanol - ethanol) at the beginning of the twentieth century using molasses as a substrate, an expensive raw material that made the process economically unfeasible. In this work, we developed a second-generation fermentation process using cellulosic sugar as the substrate. A strain of Clostridium saccharoperbutylacetonicum has been evolved to n-butanol resistance, and we have found that the addition of xylooligosaccharides to the culture medium leads to a significant increase in the n-butanol yield and productivity. As a result, an n-butanol titer of 12.5 g/L and a productivity of 0.43 g/L.h were obtained, a respective gain of 17% and 58% relative to the initial process. These advances indicate that second-generation technologies can make viable the production of renewable n-butanol.