Size matching between anvils and the pressure transmitting medium (PTM) is a key factor that affects pressure generation and sealing for a large volume cubic press. In this work, we studied the influence of PTM sizes from 30.5 mm to 34.5 mm at a fixed anvil geometry dimension (23.5 mm) on the pressure efficiency and sealing performance by measuring the pressure of the gasket and cell simultaneously at room temperature. Wires made of Bi, Tl, Ba, or Manganin were used for pressure calibration experiments within a pressure range of up to 6 GPa. It was found that a PTM with an edge length of 33.5 mm had the highest pressure-generation efficiency, but its sealing performance was the worst. Furthermore, it was confirmed that a PTM with an edge length of 32.5 mm had the best overall performance for a 23.5 mm anvil when both efficiency and sealing were considered. The results show that the pressure-generation efficiency and sealing performance are highly sensitive to PTM size. It is less rigorous to gauge the performance of the assembly only by the pressure-generation efficiency. This work provides practical guidelines and contributes to optimizing the design of the high-pressure assembly.