Many RC frame structures were severely damaged or collapsed in some layer. The phenomenon was significantly different from the expected failure mode in seismic design code. This paper comprehensively sums up the earthquake characteristics of masonry infilled RC frame structures. Based on an investigation of a masonry infilled RC frame structure damaged in the earthquake area, conduct the research on frail-layer caused by infill walls uneven decorated. On the hypothesis of keeping the main load-bearing component invariant, two models were considered, i. e. frame with floor slab, and frame with both floor slab and infill wall. Furthermore, divide them into groups of the bottom, the middle and the top frail-layer to discuss by changing the arrange of infill wall. Time history analyses using three-dimensional sophisticated finite element method were conducted. The major findings are: 1)infill walls may significantly alter the failure mechanism of the RC frames. 2)controlling the initial interlayers lateral stiffness ratio in a reasonable range is an effective method to avoid frail-layer damage. These findings suggest that the effects of infill wall should be considered in seismic design, keep the initial interlayers lateral stiffness ratio less than the paper suggested, and the structural elasto-plastic analysis model should take slabs and infill walls into account.