Uncertainty relations give upper bounds on the accuracy by which the outcomes of two incompatible measurements can be predicted. While established uncertainty relations apply to cases where the predictions are based on purely classical data (e.g., a description of the system's state before measurement), an extended relation which remains valid in the presence of quantum information has been proposed recently [Berta et al., Nature Phys. 6, 659 (2010)]. Here, we generalize this uncertainty relation to one formulated in terms of smooth entropies. Since these entropies measure operational quantities such as extractable secret key length, our uncertainty relation is of immediate practical use. To illustrate this, we show that it directly implies security of quantum key distribution protocols. Our security claim remains valid even if the implemented measurement devices deviate arbitrarily from the theoretical model.