The present disclosure provides a high-temperature negative-pressure air exchange sterilizer and a sterilization method thereof. An air inlet is disposed at a bottom of a waterproof shell of the sterilizer, and an inlet filter is installed at the air inlet. Air entering from the air inlet is divided into two paths at a check valve. One path is connected with a negative-pressure fan through a pipeline B, and the other path is communicated with an air outlet through a pipeline A. A plurality of heating rods and temperature sensors are disposed in the pipeline A. The pipeline A is zigzag disposed at an upper part of the waterproof shell, and a thermal insulation material is disposed outside a zigzag part. A butterfly valve and an outlet filter screen are sequentially disposed at the air outlet in an air exhaust direction. The problem that viruses exhaled by breathing of an infected person are mixed in aerosol, so that a person in close contact with the infected person is likely to be infected is solved. According to the present disclosure, polluted air is heated through a plurality of sections of high-temperature areas, and finally viruses are killed in a pipe, so that clean air is exhausted to the external environment; the negative-pressure fan is used to form a certain negative pressure in a room to complete an indoor air exchange; the viruses are killed quickly; and the virus killing efficiency is high.