Multifunctional nanoparticles have attracted significant attentions for oncology and cancer treatment. In fact, they could address critical point for tumour treatment by creating a stimuli-responsive targeted drug delivery system that can exist stably in the systemic circulation, efficiently penetrate the tumour tissue, and then accumulate in tumour cells in large quantities. A novel stepwise pH-responsive multifunctional nanoparticles (FPDPCNPs/DTX) for targeted delivery of the antitumour drug docetaxel (DTX) is prepared by coating a tumour acidity-sensitive “sheddable” FA modified β-carboxylic amide functionalized PEG layer (folic acid-polyethylene glycol-2,3-dimethylmaleic anhydride, FA-PEG-DA) on the cationic drug-loaded core (poly(β-amino ester-cholesterol, PAE-Chol) through electrostatic interaction in this study. The charge shielding behaviour of the FPDPCNPs/DTX was confirmed by zeta potential assay. The surface charges of the nanoparticles can change from positive to negative after PEG coating. The IC₅₀ values of FPDPCNPs/DTX was 3.04 times higher than that of PEG “unsheddable” nanoparticles in cytotoxicity experiments. The results of in vivo experiment further showed that FPDPCNPs/DTX had enhanced tumour targeting effect, the tumour inhibition rate of FPDPCNPs/DTX was as high as 81.99%, which was 1.51 times that of free DTX. Under a micro acidic environment and folate receptor (FR)-mediated targeting, FPDPCNPs/DTX contributed to more uptake of DTX by MCF-7 cells. In summary, FPDPCNPs/DTX as a multifunctional nano-drug delivery system provides a promising strategy for efficiently delivering antitumour drugs.