Polycationic gene carriers are attracting increasing attention for their use as gene delivery systems. Herein, a novel and high-performance polycationic gene carrier (i.e., Zn-DPPA2) was constructed by introducing a dipicolylamine compound along with zinc ion coordination onto polyethylenimine (PEI1.8k) via Schiff base bonds. Zn-DPPA2 exhibited efficient transfection and negligible cytotoxicity. Zn-DPPA2/DNA complexes possessed significant endocytosis efficiency and excellent endosomal escape ability. Additionally, this polycaitionic gene carrier showed an excellent ability as an antiserum. The nanoscale size and good size stability ensured that Zn-DPPA2/DNA could accumulate in tumor tissue through the enhanced permeability and retention (EPR) effect. Moreover, Zn-DPPA2/DNA complexes exhibited efficient transfection in tumor tissue after intravenous injection. This strategy provided a new idea for polycationic gene carrier construction, which has prospects for widespread application in the field of gene therapy.