This paper introduces the concept of safety-related (SR) uncertainty and the methodology to measure SR uncertainty. SR uncertainty is concerned with the effect of parameter uncertainty on the uncertainty of system unsafety (defined with respect to achieved safety integrity level), which is in direct contrast to the effect on overall system uncertainty. The properties of SR uncertainty are discussed and its significance in analyzing safety systems is highlighted. The conventional global sensitivity analysis (GSA) to handle overall uncertainty is inappropriate when SR uncertainty is of interest. We present and discuss four methods to measure SR uncertainty. Three examples are used to demonstrate the effectiveness of the proposed methods in comparison with GSA.