In this study, transferrin (Tf) conjugated distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) nanoparticles (DPT) was successfully prepared to deliver doxorubicin (DOX) to improve the chemotherapy efficacy of K562 leukemia cells. The results show that DPT were nanosized and presented spherical shaped particles, and the average particle size is about 80 nm. The DOX encapsulation efficiency of DPT was >70%. These nanoparticles could release DOX in the acid nucleus and facilitate the delivery of DOX after endocytosis. In addition, DPT is more targeted to K562 cancer cells than DSPE-PEG nanoparticles (DP). To be specific, the cytotoxic effect of DPT on cancer cells was significantly higher than that of DP, indicating that the tf modified nanoparticle system has better targeting efficiency. In summary, the results clearly show that the targeting of leukemia cells by the Tf -coupled nanoparticle system may pave the way for successful treatment of leukemia.