The therapeutic efficacy of anti-cancer nanomedicines is generally constrained due to limited accumulation in the solid tumors. In this study, we developed a biomimetic nano-carrier to enhance the chemo-therapeutic efficacy of doxorubicin and icotinib in a chemo-resistant non-small cell lung cancer (NSCLC) cell line harboring a mutation in the epidermal growth factor receptor (EGFR). The unique nanomedicine was prepared by coating with targeting cancer cell membrane proteins as highly specific ligands. The resulting biomimetic nanoparticles were highly stable and exhibited superior homologous targeting ability in vitro compared with control groups. In a mouse EGFR-mutated NSCLC xenograft model, intravenous injection of the biomimetic nanomedicine led to a high tumour inhibition rate (87.56%). Histopathological analysis demonstrated that the biomimetic nanomedicine had minimal side effects. Taken together, a cancer cell membrane-based biomimetic drug carrier can significantly enhance drug accumulation and improve therapeutic efficacy in cancers.