A method of designing model-predictive safety systems that can detect operation hazards proactively is presented. Such a proactive safety system has two major components: a set of operability constraints and a robust state estimator. The safety system triggers alarm(s) in real time when the process is unable to satisfy an operability constraint over a receding time-horizon into the future. In other words, the system uses a process model to project the process operability status and to generate alarm signals indicating the presence of a present or future operation hazard. Unlike typical existing safety systems, it systematically accounts for nonlinearities and interactions among process variables to generate alarm signals; it provides alarm signals tied to unmeasurable, but detectable, state variables; and it generates alarm signals before an actual operation hazard occurs. The application and performance of the method are shown using a polymerization reactor example.