In order to optimize Retort process for liquid newborn formula， a single factor experiment was used to screen the optimum process conditions with viscosity as the index. The optimal homogeneous pressure was 30 MPa， sterilization temperature was 115 ℃， and sterilization time was 10 min. On this basis， orthogonal experiments were used to further optimize three parameters， and the optimum process parameters were obtained as homogeneous pressure 20 MPa， sterilization temperature 115 ℃， and sterilization time 8 min， the particle size， viscosity and color difference(ΔE) of the products produced by the two process parameters are compared， the results show that the product produced by the process parameters optimized by the orthogonal experiment has better stability. By comparing the safety of the orthogonal optimized Retort liquid newborn formula with UHT liquid newborn formula， the results showed that the aerobic plate count of Retort product was 0 CFU/mL， and the number of thermophilic aerobic spores was lower. Scanning electron microscope (SEM) and laser confocal microscope (CLSM) were used to compare the microstructures of protein and fat between Retort liquid formula and UHT liquid newborn formula. Retort liquid formula protein had a denser network structure and less denaturation； the number of fat globules was more and the size was smaller. Therefore， Retort process has a better sterilization effect and is more suitable for the sterilization of liquid newborn formula， which will lay the foundation for providing safer and more nutritious breast milk substitute for newborn infants.