It is still a major challenge for targeted cancer chemotherapy to design stable biodegradable micellar drug delivery systems which show a rapid and complete intracellular drug release. Here, reversibly core-crosslinked pH-responsive biodegradable micelles were developed based on poly(ethylene glycol)-poly(2,4,6-trimethoxybenzylidene-pentaerythritol carbonate-co-pyridyl disulfide carbonate) [PEG-P(TMBPEC-co-PDSC)] copolymers and investigated for intracellular doxorubicin (DOX) release. PEG-P(TMBPEC-co-PDSC) copolymers formed micelles with a small size of 58.6 nm were readily crosslinked by the addition of dithiothreitol (DTT). Notably, in vitro release studies showed that under physiological conditions only ca. 19.9% of DOX was released from the reversibly crosslinked micelles in 24 h at a low micelle concentration of 40 μg/mL. The release of DOX was accelerated at pH 5.0 or in the presence of 10 mM glutathione (GSH) at pH 7.4, in which 64.2% and 44.1% of DOX was released, respectively, in 24 h. The drug release was further boosted at pH 5.0 and 10 mM GSH, with 98.8% of DOX released in 12 h. Moreover, DOX release was also facilitated by a 4 h incubation at pH 5.0 followed by incubation at pH 7.4 with 10 mM GSH. Confocal microscopy indicated that DOX was delivered and released into the nuclei of RAW 264.7 cells following a 12 h incubation with DOX-loaded reversibly crosslinked micelles. MTT assays revealed that DOX-loaded reversibly crosslinked micelles had much higher antitumor activity than irreversibly crosslinked controls, with low IC50 values of 1.65 and 1.14 μg/mL for HeLa and RAW 264.7 cells, respectively, following a 48 h incubation. The blank crosslinked micelles had a low cytotoxicity of up to a concentration of 0.8 mg/mL. These reversibly crosslinked pH-sensitive biodegradable micelles with superior extracellular stability but activated intracellular drug release provide a novel platform for tumor-targeting drug delivery.