Estimation of membrane fatigue lifetime under in-situ conditions involving cyclic hygro-thermal stress is of particular interest in fuel cell durability research; however, conducting experiments to study the in-situ fatigue process within membranes is often expensive and in many cases, infeasible. Here, an in-situ numerical fatigue model based on the Smith Watson-Topper (SWT) criterion is presented and validated against experimental results of membrane fatigue lifetime under humidity cycling in a fuel cell. The amplitude of strain oscillations is found to have a profound impact on the membrane fatigue lifetime. Importantly, it is also discovered that membrane fatigue failure occurs earlier under the channels than under the lands. The model is further used to simulate the membrane fatigue lifetime under operationally representative conditions of simultaneous temperature and humidity cycling where the lifetime is severely reduced due to increased amplitudes of strain oscillations. (C) 2017 Hydrogen Energy Publications LLC. Published by Elsevier Ltd. All rights reserved.