The synergic effect of eight salts on D-xylose to xylitol bioconversion by Debaryomyces hansenii NRRL Y-7426 was optimized through a central composite design (CCD) in shaker flasks. Optima conditions were then assayed using detoxified corncob hemicellulosic hydrolyzates as the carbon source, increasing the fermentative parameters to Q(P) = 0.118 g/L.h and Y-P/S = 0.45 g/g from Q(P) = 0.101 g/L.h and Y-P/S = 0.39 g/g (without supplementation). Finally, the process was successfully scaled up to a 50 L Braun Biostat D50 fermenter, since the time of fermentation was reduced from 103 h to 42.8 h and the fermentation parameters increased to Q(P) = 0.395 g/L.h and Y-P/S = 0.59 g/g using a synthetic medium and Q(P) = 0.236 g/L.h and Y-P/S = 0.39 g/g with detoxified hydrolyzates. All the results confirmed the positive influence of supplementing synthetic culture media or detoxified corncob hydrolyzates with salts for the development of D. hansenii.