PEGylated micelles have been widely used for tumour therapy. Although PEGylation can prolong the blood circulation time, there is only less than 5% of administered micelles that can be transported to tumour sites and over 95% are cleared by the reticuloendothelial system (RES). Besides, the limited intracellular drug release also restricts their efficacy. To improve the therapeutic efficacy of PEGylated micelles, a safe, simple and efficient hybrid micellar system, composed of poly(aminoethyl ethylene phosphate)-poly(L-lactic acid) (PAEEP-PLLA) and poly(ethylene glycol)-poly(L-lactic acid) (PEG-PLLA), was developed. The hybrid micelles significantly prolonged the blood circulation time by decreasing the plasma protein adsorption and reducing the clearance by the RES. The deposition of the hybrid micelles in the liver and spleen was reduced, and the tumour accumulation was greatly improved. In addition, the intracellular drug release of the hybrid micelles was obviously increased due to the easy degradation of PAEEP in the endo/lysosomes. The tumour growth inhibition efficiency of the hybrid micelles was much higher than that of the PEG-PLLA micelles (84.5% vs. 44.5%). Furthermore, the hybrid micelles exhibited low hemolysis and reduced deposition in normal organs, which revealed their excellent bio-safety. Therefore, we established a promising hybrid micelle system for efficient anti-tumour therapy.