Abstract: Firstly, the model was discussed for beam-column elements with fiber discretization to consider the in-plane and out-of-plane interactions of infill walls. Then, a shaking table test model of a 4-storey infilled RC frame was developed and analyzed via the finite element software, OpenSees. The comparison with the experimental results indicates that the numerical model considering in-plane and out-of-plane interactions of unreinforced masonry infill walls is valid for modeling the infilled RC frame structure. Finally, based on the calibrated numerical model, a three-dimensional model for the infill RC frame of a teaching building was established via OpenSees. And the static pushover analysis and incremental dynamic analysis were carried out on the model with and without considering in-plane and out-of-plane interactions of unreinforced masonry infill walls. Furthermore, incremental dynamic analysis results under 24 suites of ground motion records were used to evaluate the global collapse resistance capacity of the structure with 50% collapse probability. The comparison of the results shows that without considering in-plane and out-of-plane interactions of infill walls, the global collapse resistance capacity of the structure will be underestimated obviously.