It is important to predict the pressure loss due to hydraulic transport of large solid particles for the design of subsea mining system. The mixture flow in the lifting pipe is expected to be unsteady in the actual mining system. The authors develop the one-dimensional mathematical model to predict the pressure loss of pulsating mixture flow in a static vertical pipe assuming that the flow in the pipe is fully developed. The experiment on hydraulic transport of solid particles was carried out to obtain the data for the investigation of the effects of flow fluctuation on pressure loss in a static vertical pipe. In the experiment, alumina beads and glass beads were used as solid particles, and the experimental parameters were mixture velocity, solid concentration, pulsating period, and pulsating amplitude. The proposed model was validated by a comparison with experimental data. Furthermore, we calculated the pressure losses due to hydraulic transports of polymetallic sulfide ores and manganese nodules using the proposed model. The calculation results showed that the fluctuating component in pulsating mixture flow should be considered for the design of lifting system and that the homogeneous mixture model could not be applied to the prediction of the pressure loss unless the mixture concentration is low and the pulsating period is short.