Redox-responsive micelles based on amphiphilic polyethylene glycol-polymethyl methacrylate with the introduction of disulfide containing cross-linked agent (mPEG-PMMA-SS) were developed for intracellular drug release. Benefiting from the amphiphilicity, mPEG-PMMA-SS could self-assembled into core cross-linked micelles in aqueous medium with tunable sizes (85–151 nm), appropriate zeta potential (−24.8 mV), and desirable critical micelle concentration (CMC) (0.18 mg/mL). Doxorubicin (DOX) could efficiently load into the micelles with satisfactory entrapment efficiency. As expected, the in vitro release studies displayed that DOX release from mPEG-PMMA-SS micelles was about 75% within 10 h under tumor-relevant reductive condition, whereas only about 25% DOX was released in non-reductive medium. SRB assays indicated that these mPEG-PMMA-SS micelles were biocompatible and nontoxic up to a concentration of 50 μg/mL. The cytotoxicity studies and the intracellular drug delivery demonstrated that the drug release behavior in cells was related to the concentration of GSH in cytoplasm. Furthermore, the cell experiments using fluorescence microscopy showed clearly that DOX was delivered by micelles to the cytoplasm, released in cytoplasm under reductive environment, and then accumulated in cell nucleus. These results suggest that such redox-responsive micelles may develop into an efficient cytoplasmic delivery for hydrophobic anticancer drugs.