A detailed sensitivity and uncertainty analysis is performed for several parameters of interest in the design of the high-conversion reactor (HCR) concept. The main goals of this work are to determine the response standard deviation due to basic nuclear data uncertainties and to incorporate integral experiment information from the PROTEUS facility to reduce the computed uncertainties, where possible. The results for reactivity and five important reaction rate ratios (at the 0% void state) that are part of the measurement program in the PROTEUS phase II experiments are highlighted. In addition, the void coefficient at both low void and high void is studied. The computed correlation coefficients between the PROTEUS and HCR models are uniformly high for all responses. This indicates that a reduction in uncertainty can be achieved within the measurement uncertainty and that the PROTEUS experiments were ideal for the physics characterization of HCR responses.