The invention provides a novel high efficient aqueous printing ink cleaning agent and a preparation method thereof. The cleaning agent comprises the following components in parts by weight: 10 to 30 parts of triethanolamine, 20 to 30 parts of N-methyl pyrrolidone, 1 to 5 parts of nano particle, 10 to 30 parts of cholamine, 5 to 8 parts of benzotriazole, 5 to 20 parts of polyethylene glycol octyl phenol ether, 2 to 15 parts of surfactant, 2 to 10 parts of osmotic agent, and 5 to 40 parts of soft water. The preparation method comprises the following steps: adding a surfactant and an osmotic agent into soft water according to the formula, stirring 3 to 5 minutes to evenly mix the components; then adding nano particles, stirring for 5 to 10 minutes at a rotation speed of 500-1000 r/min; carrying out ultrasonic dispersion for 10 to 30 minutes at a temperature of 20 to 40 DEG C, then adding triethanolamine, N-methyl pyrrolidone, cholamine, benzotriazole, and polyethylene glycol octyl phenol ether in sequence, stirring, and evenly mixing. The cleaning agent has a strong performance on removing dirt such as printing ink, the cleaning efficiency is high, at the same time, the base material will not be damaged, the cleaning agent is safe to use, the toxicity is little, and the quality is the same after long term storage.