Self‐assembled polymeric nanoparticle (NP) drug carriers are capable of encapsulated and controlled delivery, facilitating improvements in the therapeutic efficiency of drugs. Here we report a series of poly(l‐glutamic acid)‐g‐methoxy poly(ethylene glycol)/4‐phenylbutyl ester (PLG‐g‐mPEG/PB) copolymers, which were synthesized by esterification of 4‐phenylbutanol (PB) and PLG‐g‐mPEG in different feed ratios. The copolymers obtained form into nano‐sized micelles in aqueous solution by a self‐assembly process, with lower critical micelle concentration value for higher PB ratio in the copolymers. Variable temperature infrared spectroscopy and circular dichroism were used to prove the breaking of intermolecular hydrogen bonds after PB modification. Podophyllotoxin (PPT), an effective anticancer agent, was incorporated into the inner core of the micelle system by physical entrapment through hydrophobic interaction between the drug and the PB‐modified copolymers. Both the drug loading content and the loading efficiency increased with PB content in the PLG‐g‐mPEG/PB copolymers and reached an ultrahigh value of 28.2 wt% and 94%, respectively. The PPT‐encapsulated micelles (PPT‐NPs) were stable at pH 7.4 but dissociated and released 80% of loaded PPT in a weak acidic environment (pH 5.0). The in vitro proliferation of non‐small‐cell lung cancer cells (A549) was significantly inhibited by PPT‐NPs in a cytotoxicity assay. These results demonstrate that hydrophobic modification is an efficient route for tuning the self‐assembly behaviour and drug encapsulation of PLG‐g‐mPEG copolymers, and our PLG‐g‐mPEG/PB will serve as a promising carrier for hydrophobic anticancer drug delivery. © 2021 Society of Industrial Chemistry.