Airbag related out-of-position occupant (OOPO) thorax injury was investigated for many years. However, little study was published to address how to reduce the OOPO related thorax injury from the point of view of restraint system design. The objective of this investigation is to utilize both experiment and computer simulation approaches to study the OOP small female thorax injury mechanism and its relationship to the restraint system design parameters. Coupled structure, computational fluid dynamics (CFD) and rigid multi-body dynamics simulations were performed to investigate the effect of airbag deployment on OOPO thorax injury. The laboratory experiments are performed to validate the simulation results. Then the relationship of airbag design parameters on OOPO thoracic injury risk is characterized. The outcomes of this study lay down the foundations for advanced restraint system development.