It is known that potential safety risks of Li-ion battery limit their applications. Thermal abuse, which is induced by internal short circuit, is the most dangerous scenario among various safety risks. Numerous studies of internal short circuit have been done by experimental approach. However, experimental methods cannot provide sufficient information to show the mechanism of thermal runaway propagation during internal shorting. Recently, a comprehensive three-dimensional safety model for Li-ion cell, which is based on a multiscale multi-dimensional (MSMD) battery modeling methodology, has been developed by energy storage group in NREL. This safety model, which includes three sub-models, provides a unique capability to investigate the effects of internal short circuit on thermal runaway propagation in a Li-ion battery. In term of sub-models, electrochemical model is used to simulate electrochemical reaction of Li-ion battery; internal short circuit model and thermal abuse model are used to predict the behavior of thermal runaway. In this study, three-dimensional simulations with internal short circuit have been done by applying the safety model. The numerical approach was validated by an experiment utilizing an internal short circuit device, and the results were analyzed in time domain and frequency domain. The mechanism of thermal runaway propagation was discussed, and the dominant parameters to lead thermal runaway were identified. The simulation results reveal the behavior of thermal runaway is affected by initial short volume and short resistance as well as electrical resistance of the electrodes.