In this work, the SnO2/SiO2 materials with various Sn loadings ranging from 1 to 16 wt % were prepared and used as heterogeneous acid catalysts for soybean oil transesterification to produce biodiesel. The catalyst with 8 wt % Sn loading and calcined at 873 K exhibited the best catalytic activity, giving an oil conversion of 81.7%. The dispersed amorphous SnO2 species on the silica surface are considered to be active sites for the transesterification reaction. The effect of reaction parameters such as catalyst amount, reaction temperature, reaction time, and methanol-to-oil ratio was investigated to optimize the transesterification conditions. It is shown that the free fatty acid (FFA) and water have no significant influence on the catalytic activity to the transesterification reaction. In addition, the heterogeneous acid catalyst was found to have high activities toward the esterification of FFAs. Furthermore, the catalyst could be recovered with a better reusability.