In-box LOCA was identified as one of the worst accidental scenarios for the HCLL TBS (Helium Cooled Lithium-Lead Test Blanket System). Aiming to experimentally analyze the consequences of this transient, ENEA designed and built THALLIUM (Test HAmmer in Lead LIthiUM), a facility that reproduces the LiPb loop of the HCLL TBS. Two experimental campaigns were carried out by simulating the rupture of a stiffening plate and the related helium injection in the LiPb loop. The obtained experimental data were used to check the capabilities of RELAP5 system code to reproduce the pressure wave propagation that follows this accident. The first simulations were made with RELAP5-3D using LBE (Lead–Bismuth Eutectic) as a system fluid, as the thermophysical properties of LiPb are tabulated only up to a maximum value of 40 bar in this version of the code. Then, LiPb properties were implemented in RELAP5/mod3.3, after selecting the proper correlations from a literature review. This work summarizes the numerical simulations of the second experimental campaign, which was simulated with both versions of the code. The simulations highlight that the code is able to accurately reproduce the experimental results and that RELAP5-3D is slightly more precise than RELAP5/mod3.3 in predicting the pressure trends.