In this work, we investigate the improvement in piezoelectric performance of ZnO nanowires film by chemical doping and interfacial modification strategy. The Cl-doped ZnO nanowires films were synthesized by a modified hydrothermal approach and characterized by SEM, EDX, XRD, PL, XPS, TEM and I-V characterization. The effect of Cl-dopant with different doping concentration has been demonstrated by an improvement of the piezoelectric output performance due to the induced lattice strain along the ZnO c-axis, which significantly facilitates the piezocharges separation under the applied stress. The experimental results indicate the existence of lattice strain along doped ZnO nanowire polar axis resulted from the different ionic size between Cl and O. More importantly, by preparing Cl-doped ZnO nanowire film on the p-type CuO film, our experimental results reveal that the piezoelectric output voltage and current of Cl-doped ZnO nanowire film can be further enhanced due to CuO can reduce electron screening effect. We demonstrate that the utilization of chemical doping and interfacial modification can be considered as a compatible strategy for realizing high performance energy harvesting device.