Taken together, these data clearly show that siRNA@PLGA NPs can efficiently overcome the drug-resistance in the MDR SKOV3-TR and A2780-CP20 cells, and also indicate the simultaneous inhibition of both genes is more efficient to enhance the cytotoxicity of chemotherapeutics on the resistant ovarian cancer cells, compared with the single inhibition of either MDR1 or BCL2 genes. This evidence concerns the gene ABCB1 and ovarian carcinoma.