The invention relates to an ultrasonic nano spray liquid preparation, which is prepared from the following components in parts by weight: 1-10 parts of coenzyme Q10, 1-100 parts of hyaluronic acid, 1-20 parts of an oil phase material, 2-20 parts of an emulsifier, 1-100 parts of a co-emulsifier and 100-10000 parts of ethanol and/or water, wherein the oil phase material is one or a combination of more of medium chain triglyceride (MCT), vitamin E and soybean oil; the emulsifier is one or a combination of more of castor oil polyoxyethylene ether, hydrogenated castor oil poly(hydrocarbon oxygen ester) 40 and Tween-80; the co-emulsifier is one or a combination of more of diethylene glycol monoethyl ether, labrasol and caprylic capric triglyceride. The invention also provides a preparation method of the ultrasonic nano spray liquid preparation; the method comprises the following steps: evenly mixing the oil phase material, the emulsifier, the co-emulsifier and the coenzyme Q10 so as to obtain a mixed oil phase; dissolving hyaluronic acid into a solvent to obtain a water phase; dispersing the mixed oil phase into the water phase, and carrying out ultrasonic dispersion. The ultrasonic nano spray liquid preparation is stable in performance; nanoscale fine fogdrops are enabled to permeate the skin deep in a form of ultrasonic spray, so that the skin absorption of the coenzyme Q 10 and the hyaluronic acid is improved.