The application of nano drug delivery systems (NDDSs) may enhance the effectiveness of chemotherapeutic drugs in vivo. However, the short blood circulation time and poor drug release profile in vivo are still two problems with them. Herein, by using red blood cell membrane (RBCm) wrapping and pH sensitive technology, we prepared RBCm wrapped pH sensitive poly(l-γ-glutamylcarbocistein)-paclitaxel (PGSC-PTX) nanoparticles ([email protected] NPs), to prolong the circulation time in blood and release PTX timely and adequately in acidic tumor environment. The PGSC-PTX NPs and [email protected] NPs showed spherical morphology with average sizes about 50 and 100 nm, respectively. The cytotoxicity of [email protected] NPs was considerably decreased compared with that of PGSC-PTX NPs. PTX release from PGSC-PTX and [email protected] NPs at pH 6.5 was remarkably higher than those at pH 7.4, respectively. The [email protected] NPs exhibited remarkably decreased uptake by macrophages than PGSC-PTX NPs. The area under the curve within 72 h (AUC0-72h) for is significantly higher than PGSC-PTX NPs. The [email protected] NPs also showed significantly stronger growth-inhibiting effect on tumor than PGSC-PTX NPs. These results indicated that [email protected] NPs have acidic drug release sensitivity, the characteristics of long circulation, and remarkable tumor growth inhibiting effect. This study may provide an effective strategy for improving the antitumor effect of NDDS.