Genome editing mediated by CRISPR/Cas9 is an attractive weapon for cancer therapy. However, delivery of CRISPR/Cas9 components to achieve therapeutic efficiency is still challenging. Herein, a quaternary ammonium-functionalized poly(L-lysine) and a cholesterol-modified PEG (QNP) were self-assembled with a negatively charged CRISPR Cas9/sgRNA ribonucleoprotein (RNP) to form a ternary complex (QNP/RNP). Such a delivery system of QNP exhibited multiplex genome editing capabilities (, the gene and the gene). In addition, QNP/RNP containing PLK1 sgRNA led to 30.99% of genome editing efficiency in MCF-7 cells with negligible cytotoxicity of the carrier. QNP/RNP, which was capable of simultaneously inhibiting cell proliferation, mediating cell cycle arrest and downregulating expression of PLK1, held great therapeutic efficiency. Moreover, QNP/RNP exhibited outstanding accumulation in tumors and high biocompatibility . In an MCF-7 xenograft animal model, QNP/RNP showed excellent anti-tumor efficacy and achieved 17.75% indels ratio. This work showcases the successful delivery of CRISPR Cas9/sgRNA RNP with enhanced genome editing efficiency and provides a potential on-demand strategy for cancer therapy.