The use of a liquid-piston system for hydrogen compression is investigated in this paper by means of a computational fluid dynamics (CFD) analysis. In the specific context of hydrogen-driven vehicles, high-pressure storage tanks are key to provide substantial range. The present study focuses on the intermediary compression stage of a compression-storage-dispensing (CSD) station, bringing hydrogen gas from 15 bar to 450 bar, i.e., for a pressure ratio of 30. Until now the liquid-piston technology has not been investigated for hydrogen gas compression at very high pressure, which is the purpose of this study. Simulations of the compressible two-phase flow problem are performed with a volume-of-fluid (VOF) framework using a real gas model for the gaseous phase to account for compressibility effects at large pressure ratios. A particular attention is paid to the numerical model formulation and to the treatment of the thermal boundary conditions. Results are reported using both time-resolved instantaneous bulk thermodynamic variables and global integrated quantities. Different compression scenarios are investigated, which highlights the compromise between compression efficiency and power density. To achieve the targeted pressure ratio at a power density of approximately 540 kW/m, the compression energy cost reaches 1.67 kWh/kg. Finally the paper proposes an innovative solution to minimise cost and achieve quasi-isothermal compression, based on internal forced convection. For a similar power density, a high-speed fan in the top part of the compression chamber (modelled as a volumetric momentum source of 2500 N/m) increases heat transfer and leads to a 25-% reduction in compression consumption.