Polyethylene glycol (PEG)-based block copolymer micelles and hyaluronic acid (HA)-based grafted copolymer micelles have been widely investigated in chemotherapy. In this study, to evaluate the differences among HA-based grafted polymer micelles, PEG-based block polymer micelles and the mixed of these two micelles in enhancing antitumor effects and overcoming MDR, two amphiphilic vitamin E succinate (VES) derivatives, HA VES (HA-g-VES) and PEG 2000 VES (TPGS2k), were applied as nanocarriers to prepare HA-VES micelles (HA-PMs), TPGS2k micelles (TPGS2k-PMs) and the mixed micelles (HA/TPGS2k-PMs) for the co-delivery of doxorubicin (DOX) and curcumin (Cur). With the addition of TPGS2k, the particle size of HA/TPGS2k-PMs (153.37 ± 1.00 nm) was smaller than that of HA-PMs (223.83 ± 1.84) but significantly larger than that of TPGS2k-PMs (about 20 nm). The loading efficiency of HA/TPGS2k-PMs was 7.10%, which was lower than HA-PMs (8.31 ± 0.15%) but higher than TPGS2k-PMs (4.38 ± 0.24%). In vitro, HA/TPGS2k-PMs and TPGS2k-PMs exhibited higher cytotoxicity and reversal MDR effects than HA-PMs in MCF-7/Adr cells. However, HA/TPGS2k-PMs, HA-PMs and TPGS2k-PMs all significantly improved the tumor biodistribution, the antitumor effects and reduced the side effects of DOX in 4T1-tumor-bearing mice, but these three micelles displayed no differences in vivo. Therefore, EPR passive targeting effects caused by PEGylated micelles and CD44 active targeting effects caused by HA-based micelles have no significant variance in the delivery of antitumor drugs by i.v.