The properties of nuclear fuel depend on the actual isotopic composition which develops during a reactor operation. In practice, the prediction accuracy of burnup calculations serves as the basis for the future precise estimation of a core lifetime and other safety-based core characteristics. The present study quantifies nuclear data induced uncertainties of nuclide concentrations and multiplication factors in water–water energetic reactor (VVER)-440 fuel depletion analysis. The well-known SCALE system and the TRITON sequence are used with the NEWT deterministic solver in the SAMPLER module that implements stochastic techniques to assess the uncertainty in computed results. The propagation of uncertainties in neutron cross section and fission yields is studied through the depletion calculation of 2D heterogeneous VVER-440 fuel assembly with an average enrichment of 4.87 wt % of 235U and six gadolinium rods with 3.35% of Gd2O3. In the paper, fixed nominal depletion conditions are based on the real operational data of the Slovak nuclear power plant Bohunice unit 4 during cycle 30. In total, 250 cases with uncertain parameters are computed and the results are evaluated by an auxiliary tool.