It is widely accepted that Ultra-High Performance Concrete (UHPC) could be designed by the employment of Modified Andreasen and Andersen (MAA) particle packing model. However, the traditional MAA model only takes into account that dry particles reach the dense packing status under physical conditions, without considering the chemical hydration of wet cement particles. To solve this problem, this study adopts a physicochemical packing method to optimize the mix-design of UHPC through establishing a new equivalent particle size distribution of hydrated cement by applying a multilayer spherical shell model. Based on this, the mix proportion of UHPC is redesigned and the properties of the optimized UHPC are evaluated afterwards. The results show that the optimized mix-design leads to higher particle packing density of UHPC, thereby improving the durability on the premise of guaranteeing the workability and mechanical properties. Meanwhile, the optimized mix-design can also achieve denser micro structures of UHPC matrix, which provides a valuable reference to design UHPC more scientifically and reasonably.