A facile method for synthesis of poly ethylene glycol (PEG)-armed hyperbranched polyoxetanes is presented along with characterization and use in drug delivery. A series of hyperbranched polyoxetanes with multiple PEG arms were synthesized via a one-pot cationic ring-opening polymerization of 3-ethyl-3-hydroxymethyl oxetane (EHMO) and its PEGylated derivative (EPMO), in which the feed mass ratio of EHMO to EPMO was 98:2, 96:4, 74:26, or 17:83. Characterization methods included nuclear magnetic resonance, dynamic light scattering, Fourier transform infrared, differential scanning calorimetry, and scanning electron microscopy. Toxicity of the synthesized polymers to human dermal fibroblasts was evaluated using the MTT assay. Formulation into particles was carried out to encapsulate the anticancer drug camptothecin using the single oil-in-water solvent evaporation method. The resulting drug encapsulated particles were evaluated for antitumor activity using HN12 cells.