To implement the seismic design principle of “strong column and weak beam”，frame structure with local slot in floor slab is designed, where the continuous slot penetrating through the slab along the beam ends was set to separate the longitudinal reinforcement in the slab from the beam ends. Based on the probabilistic seismic demand analysis method, frame structure with local slot in floor slab was investigated. To investigate the accuracy of numerical model, shaking table test data was utilized to verify the calculated data of frame structure with local slot in floor slab modelling by the finite element software, OpenSees. The numerical models of frame structure without slab, conventional frame structure with cast-in-place slab, and frame structure with local slot in floor slab were established subsequently. Seismic performance was studied to explore the effect of the local slot of floor slab in the viewpoint of probability based on the probabilistic seismic demand analysis，which used 22 seismic ground motions. The results showed that the cast-in-place floor slab decreased the seismic performance. Besides，the slot in floor slab weakened the adverse influence of cast-in-place floor slab and increased the seismic performance and collapse-resistant capacity of frame structure.