New polymeric biomaterials and nanomedicines targeting cancer cells are highly required because of their potential clinical applications. Gene therapy enjoys high popularity as advanced therapy due to its high specificity; however, clinical translation is scarce because the lack of efficient and safe delivery methods. Here we address the design and development of a new nanosized targeting system consisting on Cetuximab-conjugated micelles (PM) of Pluronic® F127 (F127) and Gelatin for efficient delivery of small interfering RNA (siRNA) into epidermal growth factor receptor (EGFR) overexpressing breast cancer cells. Chemical modification by carboxylation of F127 is required prior to conjugation with Cetuximab and PM development. PM presenting appropriate physicochemical features (<40 nm) and an efficiently modified surface with Cetuximab were generated. Gelatin garnished the system with the cationic groups (ζ = +30 mV) essential for the complexation of siRNA, allowing high entrapment efficiency, and an efficient gene silencing of 70% with low cytotoxicity and proper hemocompatibility. Cetuximab-functionalized PM showed higher rate of cell internalization in EGFR expressing cells than non-functionalized PM, making them a new promising tool for targeted breast cancer treatment.