Poly(2,6-dimethyl-1,4-phenylene oxide)/polyamide 6 (PPO/PA6 30/70) blends were impact modified by addition of three kinds of maleated polystyrene-based copolymers, i.e., maleated styrene-ethylene-butylene-styrene copolymer (SEBS-g-MA), maleated methyl methacrylate-butadiene-styrene copolymer (MBS-g-MA), and maleated acrylonitrile-butadiene-styrene copolymer (ABS-g-MA). The mechanical properties, morphology and rheological behavior of the impact modified PPO/PA6 blends were investigated. The selective location of the maleated copolymers in one phase or at interface accounted for the different toughening effects of the maleated copolymer, which is closely related to their molecular structure and composition. SEBS-g-MA was uniformly dispersed in PPO phase and greatly toughened PPO/PA6 blends even at low temperature. MBS-g-MA particles were mainly dispersed in the PA6 phase and around the PPO phase, resulting in a significant enhancement of the notched Izod impact strength of PPO/PA6 blends from 45 J/m to 281 J/m at the MBS-g-MA content of 20 phr. In comparison, the ABS-g-MA was mainly dispersed in PA6 phase without much influencing the original mechanical properties of the PPO/PA6 blend. The different molecule structure and selective location of the maleated copolymers in the blends were reflected by the change of rheological behavior as well.