Underwater mission payload deployment technology holds significant promise for long-term unmanned underwater construction, with large autonomous underwater vehicles (AUVs) serving as a crucial means for payload deployment. This paper employs computational fluid dynamics (CFD) numerical methods, utilizing the Reynolds-Averaged Navier‒Stokes (RANS) approach to solve the turbulence model, and simulates the separation process between the mission payload and the AUV through the dynamic fluid-body interaction (DFBI) model and overlapping mesh technology. The analysis focuses on two common mission payload layout forms and examines how different AUV deployment hatch positions affect the separation safety of mission payloads. The simulation results indicate that the built-in payload compartment arrangement substantially reduces direct drag. With forward placement, the mission payload separates more quickly, exhibits a smaller longitudinal inclination angle than other methods, and achieves a smoother separation attitude. The mission payload deployment hatch in the forward position is suitable for the mission requirements of low-speed dynamic deployment of AUVs and ensures fast and smooth separation of mission payloads.