A facile and selective route for O-alkylation of highly hydrophilic, multifunctional hyperbranched polyglycerol (PG) under non-aqueous phase transfer catalyzed conditions in dimethyl sulfoxide was developed, through which several kinds of groups were introduced onto PG. A facile and selective route for O-alkylation of highly hydrophilic, multifunctional hyperbranched polyglycerol (PG) under non-aqueous phase transfer catalyzed conditions in dimethyl sulfoxide was developed, through which several kinds of groups were introduced onto PG.