Abstract: To study the progressive collapse resistance of RC spatial beam-slab structures with unequal spans, the refined model of a spatial frame structure with key column failure was established by using the finite element software ABAQUS. The test substructure was simulated by the pushdown analysis method. The influence of the key column failure location, beam slab parameters, slab damage performance and beam end section internal force on the collapse capacity were analyzed. The results show that the slab provided 40%~50%, 20%~30%, and 15%~25% of the strength of the structure upon the failure of an interior, an exterior, and a corner column, respectively. The larger the beam span, the lower the strength of the column after failure. There was "hysteresis" in the structure of equal spans as compared with that of unequal spans. The transverse constraint had little effect on the strength of the structure without slabs. The parameters of the beam and slab had an important effect on the strength and ductility of the structure. The damage performance of the slab under small deformation could reflect the yield mode of the slab, and thus the distribution of slab cracks could be inferred. Finally, a strength calculation formula considering the influence of the slab with unequal spans was proposed.