[en] The CEA, in collaboration with EDF and AREVA-NP, is developing a core modelling tool called NEPHTIS, for Neutronic Process for HTGR Innovating Systems and dedicated at present day to the prismatic block-type HTGR (High Temperature Gas-Cooled Reactors). Due to the lack of usable HTGR experimental results, the confidence in this neutronic computational tool relies essentially on comparisons to reference or best-estimate calculations. In the present analysis, the Aleppo deterministic transport code has been selected as reference for validating core depletion simulations carried out within NEPHTIS. These reference calculations were performed on fully detailed 2D core configurations using the Method of Characteristics. The latter has been validated versus Monte Carlo method for different static core configurations [1], [2] and [3]. All the presented results come from an annular HTGR core loaded with uranium-based fuel (15% enrichment). During the core depletion validation, reactivity, reaction rates distributions and nuclei concentrations have been compared. In addition, the impact of various physical and geometrical parameters such as the core loading (one-through or batch-wise reloading) and the amount of burnable poison has been investigated during the validation phases. The results confirm that NEPHTIS is able to predict the core reactivity with uncertainties of ±350 pcm. At the end of the core irradiation, the U-235 consumption is calculated within ± 0, 7 % while the plutonium mass discharged from the core is calculated within ±1 %. As far as the core power distributions are concerned, small discrepancies ( and < 2.3 %) can be observed on the fuel block-averaged power distribution in the core. (authors)