During the production of deepwater wells, downhole perforation safety is one of the key technical problems. The perforation fluctuating pressure is an important factor in assessing the wellbore safety threat. Due to difficulty in describing the downhole perforation pressure by using the existing empirical correlations, a prediction model based on data fitting of a large number of numerical simulations has been proposed. Firstly, a numerical model is set up to obtain the dynamic data of downhole perforation, and the exponential attenuation model of perforation pressure in the wellbore is established. Secondly, a large number of numerical simulations have been carried out through orthogonal test design. The results reveal that the downhole perforation pressure is logarithmic to the total charge quantity, increases linearly to the wellbore initial pressure, shows an exponential relationship with downhole effective volume for perforation, and has a power relationship with the thickness of casing and cement as well as formation elastic modulus. Thirdly, the prediction of perforation peak pressure at different positions along the wellbore agrees well with the field measurement within a 10% error. Finally, the results of this study have been applied in the field case, and an optimization scheme for deepwater downhole perforation safety has been put forward.