Amphiphilic P(MMI-co-OEG) copolymers were synthesized by using oligo(ethylene glycol) methacrylate (OEGMA) and monomethyl itaconate (MMI) with various feed ratio via free radical polymerization in bulk. The copolymer compositions were determined by 1H NMR. The copolymers self-assembled as spherical micelles by dialysis method, and the core–shell structure was confirmed by 1HNMR analysis. Self-assembly and pH- and temperature-stimuli responsive of copolymers were studied by UV-vis transmittance, fluorescence spectroscopy, TEM and DLS. LCST and pH-triggered phase transitions were influenced by environmental conditions (pH and temperature) and copolymer composition. The critical micelle concentration (CMC) of copolymeric micelles with different molar ratios (7/1, 5/1 and 3/1) were about 0.8, 0.5 and 0.03 mg/L, respectively. By increasing temperature, size of micelles decreased moreover by decreasing OEG contents in copolymers, micelles size decreased due to increase hydrophobic interactions. Naproxen was selected as model anti-tumor drug and drug-loaded micelles were prepared. High drug loading efficiencies (about 62%) were observed in copolymer with low OEG contents. Effects of pH, temperature and the copolymer composition on in-vitro drug release behavior were investigated. Cytotoxicity measurement by MTT assay indicated that no obvious cytotoxicity against HeLa cells was observed even when concentration of micelles raised. IC50 values of the naproxen and naproxen-loaded P(MMI-co-OEGMA) micelles were determined about 3.7 and 4.81 mM, respectively. These studies implied that the proposed copolymers could produce nontoxic and stable nanocarriers with controllable drug release profiles at target tissues (pH 4.5 and 7.4) by controlling the copolymer composition.