Lipase-catalyzed transesterification for biodiesel production is clean, effective and water tolerance compare with conventional chemical or physical biodiesel synthesis methods. Therefore, in the present research, Burkholderia cepacia lipase was immobilized onto mesoporous silica/iron oxide magnetic coreshell nanoparticles for canola waste cooking oil (WCO) conversion to biodiesel. Response Surface Methodology (RSM) with Central Composite Design (CCD) was used to optimize the transesterification parameters. A quadratic polynomial equation was obtained for biodiesel yield by multiple regression analysis. Desirability function approach gave the optimal transesterification condition as: immobilized lipase concentration of 36%, reaction time of 25 h, methanol to WCO molar ratio of 6.2 and reaction temperature of 34 C. The predicted biodiesel yield was 92% at the optimal condition. Transesterification catalyzed by the immobilized lipase carried out three times repeatedly, by losing just 11% of lipase activity in the third cycle of the transesterification.