“Off-targeting” and receptor density expressed at the target sites always compromise the efficacy of the nanoparticle-based drug delivery systems. In this study, we isolated different cell membranes and constructed cell membrane-cloaked biogenic nanoparticles for co-delivery of antitumor paclitaxel (PTX) and multidrug resistance (MDR)-modulator disulfiram (DSF). Consequently, MDR cancer cell membrane (A549/T)-coated hybrid nanoparticles (A549/T CM-HNPs) selectively recognized the source cells and increased the uptake by ninefold via the homotypic binding mechanism. Moreover, the A549/T CM-HNPs sensitized MDR cells to PTX by suppressing P-glycoprotein (P-gp) activity by 3.2-fold and induced effective apoptosis (70%) in homologous A549/T cells. Cell-membrane coating based on the “homotypic binding” is promising in terms of promoting the accumulation of chemotherapeutics in MDR cells and killing them.