The aim of this study was to set the reaction conditions of the photoinduced reforming of glycerol aqueous solution over Pt/hex-CdS under visible light irradiation for enhancement of hydrogen production by using a fractional factorial experimental design followed by a Box-Behnken design. The parameters assessed were irradiation time, mass of photocatalyst, concentration of glycerol, pH and electrolyte concentration (NaCl). The preliminary two-level fractional factorial design (2(5-1)) showed that all of the investigated factors have significant effect in hydrogen production, being pH the most important parameter. The three factors Box-Behnken design showed maximum response for hydrogen production in pH 4.0, 55% glycerol and 1.5 molL(-1)NaCl. The amount of hydrogen obtained under these conditions was 270% higher than our previous result, using the same photocatalyst and electron donor. In the ideal pH, >CdSH(2)(+)and >CdOH species are predominant before irradiation, indicating that such species play an important role in the primary steps of the photoelectrochemical mechanism, which served as the basis for proposing a mechanism for hydrogen generation as well as glycerol photooxidation. Based on the surface response [NaCl] x [glycerol], a solution with salinity equivalent to approximately the natural seawater was tested and the result for hydrogen production was comparable to the best condition; besides, under this condition, the solubility of CdS in aqueous solution is reduced. Copyright (C) 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.