The invention discloses an ozone sterilization device which comprises a shell, an ozone generator, a control computer and a sterilization bag. The ozone sterilization device is characterized in that an attraction pipe and a suction pipe are arranged on the shell; the sterilization bag is used for storing to-be-sterilized articles; openings are formed in two ends of the sterilization bag; the opening in one end is communicated with an ozone pipe so as to introduce ozone into the sterilization bag; the opening in the other end is commutated with the suction pipe so as to exhaust the exhausted ozone gas. The method comprises the following steps of: (a) placing the to-be-sterilized articles; (b) connecting the pipes; (c) setting sterilization parameters and starting sterilization; (d) establishing a negative pressure environment; (e) introducing the ozone; (f) carrying out pressure detection; (g) carrying out sterilization time judgment; (h) carrying out ozone concentration judgment; and (i) evacuating the ozone. According to the device and the method, the problem that a large medical device cannot be effectively sterilized is solved; the ozone in the sterilization bag is maintained at relatively high concentration; the microorganisms on the articles can be thoroughly and permanently eliminated; no zone is released; the environmental pollution is avoided.