The new silylant agent 3-(N,N′-dicyclohexylguanidine)-propyltrimethoxysilane (GPMS) was prepared straightforwardly in high yield by the simple reaction between 3-aminopropyltrimethoxysilane and dicyclohexylcarbodiimide. This new organosilane containing the basic dicyclohexylguanidine group covalently attached on silica gel is an efficient heterogeneous catalyst for the production of biodiesel. Conversions up to 98% were obtained for soybean oil methanolysis at 353 K for 3 h. This catalytic system was transposed to a semi-pilot scale in a continuous flow reactor and gave 44% conversion. The calculated activation energy of the methanolysis in this continuous system indicated that the reaction is probably under mass transfer limitations.