Herein, we synthesized PLGA nanoparticles (PLGA NPs) as a co-delivery nanocarrier for MDR1 and BCL2 siRNA by using poly-L-lysine (PPL) as a complexing reagent, and demonstrated that siRNA-loaded PLGA nanoparticles (siRNA@PLGA NPs) could efficiently elicit the simultaneous suppression of drug efflux and anti-apoptosis in the relation of mutual dependence on MDR ovarian cancer cells. This evidence concerns the gene BCL2 and ovarian cancer.