Structural manipulation of layered double hydroxide (LDH) via doping strategy has always been an effective method to achieve high catalytic performance. Herein, a novel the nickel (Ni) doping layered double hydroxide (LDH), named Ni/CuMgFe LDH, was synthesized by the impregnation method. The doping of Ni causes the lattice expansion (a and b axes stretches to 5.26 Å and 5.78 Å from 3.12 Å) and oxygen vacancies (Ovs) of LDH (30.72%). The electrochemical impedance spectroscopy (EIS) results indicates the electrons transfer ability of Ni/CuMgFe LDH have been enhanced by Ovs. The superior catalytic activity of Ni/CuMgFe LDH on benzotriazole (BTA) degradation was proved (88.9% after 6 cycling experiments) under ambient temperature and pressure. In the catalytic process of Ni/CuMgFe LDH, the oxidative and reductive species were present. A two-pathway degradation mechanism was proposed according to the LC-MS results and Hirshfeld charges of BTA. The nucleophilic reaction was present in anaerobic condition attacked by ·O2− and·H and electrophilic reaction was present in aerobic condition attacked by ·OH. This study provides a method of developing more multi-substance adsorption sites and higher electrons transfer ability via atom doping, which further allows researchers to gain new catalyst into the pollution control in complex wastewater treatment.