In the actual application environment, the probability of underwater multi-point initiation is very high. The research of multi-point explosion characteristics is of great reference value for the advancement of protection technology for personnel and equipment. For the square-distributed four-charge structure, the multi-peak pressure gain and pulse gain of the square-distributed charge and the single-charge were calculated and compared by measuring the explosion pressure perpendicular to the axis of the distribution surface, and the explosion time difference of each explosive was recorded for calibration simulation results. Then the influence of non-reflective boundary conditions on the numerical simulation of LS-DYNA asynchronous explosion was discussed, and the computational domain size which can reduce the boundary reflection and accurately simulate the multi-peak shock wave was determined by using the virtual source method. The synchronous explosion and the underwater non-synchronous explosion corresponding to the test condition were simulated by the programmed detonation method. The peak time and waveform of the test curve are in good agreement with the numerical simulation curve. The error of the peak pressure ranges from −40.68% to −2.680%, and the influence of the refined mesh size on the peak pressure is hardly more than 5%. The experimental results show that due to the large non-synchronous initiation time difference caused by the random error of the initiation system and the charge, the overpressure gain along the symmetry axis of the four charges will be less than 30%, and the impulse gain will be between 13.10% and 22.35%. Under the ideal synchronous explosion condition, the overpressure gain along the symmetry axis can reach 200%. The research results have a certain significance for the protection design of underwater equipment under extreme load conditions.