In response to the performance and construction challenges of steel trusses, a novel composite floor system composed of steel box girders and slotted laminated slabs is proposed. Compared with the truss composite floor system, the beam height is reduced by 18.8% to 24.4%. A finite element model was established to analyze the overall structural behavior of the two schemes. The results showed that the natural vibration characteristics of the structure with truss beams were similar to those with steel box girders. Under frequent earthquakes, the maximum inter-story drift angles of the steel box girder-concrete laminated slab composite floor system in the X and Y directions were 1/992 and 1/846, respectively, which were smaller than those of the truss composite floor system. Under rare earthquakes, the maximum elastic-plastic inter-story drift angles in the X and Y directions were 1/219 and 1/210, respectively, which were larger than those of the truss composite floor system. Nonetheless, the seismic performance of both systems met the requirements of Code for Seismic Design of Building(GB/T 50011-2010). An analysis of floor comfort for both systems indicated that the indicators were essentially the same, demonstrating that the steel box girder-concrete laminated slab composite floor system significantly reduces beam height while meeting the structural seismic and floor comfort requirements.