The present disclosure provides a pathogen inactivation method, which is low-frequency sonication together with illumination of a photosensitizer-containing blood sample; and the low-frequency sonication is conducted at a frequency of 15-500 KHz. Through the combination of sonication and photochemical pathogen inactivation technology that enhance and complement each other, the blood pathogen inactivation method provided by the present disclosure enhances a pathogen inactivation effect, reduces a dosage of the photosensitizer, photosensitizer-related blood quality damage, energy demand for the illumination, and pathogen inactivation treatment time, increases the blood illumination thickness for effective pathogen inactivation, saves illumination bag materials, shortens the size of illumination equipment, saves costs, and helps the pathogen inactivation technology go to the market.