Abstract: The new sterilization technologies of high efficiency and low effect on nutritional components have been widely concerned.The reconstituted milk, was inoculated with Salmonella, and sterilization effects of thermos-sonication treatment were studied.The physicochemical parameters of pre-and post-treatment were also analyzed in this study.The results showed that the significance order of factors affecting the killing logarithm value was: ultrasonic temperature, ultrasonic time, and ultrasonic power.Taking 5.0 killing logarithm value ( the percentage of killing rate was 99.999% for Salmonella) as reference, the optimal sterilization conditions were: ultrasonic time of 8.8 min, ultrasonic power of 307 W, and ultrasonic temperature of 50 ℃.Under these conditions, the physicochemical parameters did not change obviously, and the diameter of fat globules was reduced remarkably ( p < 0.05) , only 17.86% of pre-treatment sample.Therefore, it indicates that the thermo-sonication technique has huge potential for application as a sterilization method in liquid milk industry.