A mesoporous nanosized KF/CaO-MgO catalyst was prepared by coprecipitation method, and was characterized by transmission electron microscopy, X-ray diffraction, nitrogen adsorption and laser confocal Raman microspectroscopy. The catalyst possessed a unique mesoporous structure with pore size of ca. 34 nm and the average particle size of ca. 35 nm. In comparison with CaO and KF/CaO catalyst, the as-prepared catalyst exhibited higher catalytic activity, higher resistance to saponification, and better acidoresistance (10 mg KOH/g oil). The factors affecting on transesterification were also investigated, and a desired biodiesel yield over 95% was obtained under an optimal preparation conditions.