Lymphoma is one of the most common malignancies of blood system, and drug resistance is an important cause of treatment failure. Multidrug resistance gene P-glycoprotein (P-gp) plays an important role in lymphoma chemotherapeutic drug resistance. Our previous studies have found that P-gp is highly expressed in doxorubicin-resistant lymphoma cells (Daudi/R). With the development of nanotechnology, a large number of nanomaterials have been applied in various biomedical fields. Therefore, in this study, P-gp inhibitor tariquidar (TAR) and chemotherapy drug doxorubicin were loaded onto gold nanoshells (AuNSs) to construct TAR-AuNSs/Dox nanodrug system. TAR and Dox were slowly released from TAR-AuNSs/Dox in an acidic tumor microenvironment. TAR-AuNSs/Dox increased the uptake of Dox by drug-resistant lymphoma cells and inhibited P-gp expression to reduce Dox pumping. Compared to the free Dox, TAR-AuNSs/Dox had a stronger killing effect on Daudi/R cells, which provided a new therapeutic strategy for the treatment of drug-resistant lymphoma.