In the present work, mesoporous silica supported heteropolyacid salts were studied systematically for glycerol acetalization with formaldehyde. Attention was focused on finding an appropriate loading of Cs2.5H0.5PW12O40 (Cs-2.5) on mesoporous silica supports and studying the influence of the architecture of mesoporous silica on activity. Supported Cs2.5H0.5PW12O40 on 2D (SBA-15) and 3D (KIT-6 and SBA-16) pore lattice mesoporous silicas have been compared. The activity of all supported Cs-2.5 catalysts was found superior to that of bulk Cs-2.5 owing to the high surface area of the mesoporous supports. While the activity difference between 2D and 3D supports did not meet expectations, mesopore volume had a significant impact on activity, which is attributed to a good access to Cs2.5H0.5PW12O40 acid sites. The catalysts could be reused for three times (24 h each time), loosing only 10% glycerol conversion.