As a special kind of ground motion, the damage of long-period ground motion to structures has attracted the attention of scholars at home and abroad. Ten typical long-period ground motions from KiK-net and K-NET networks and ten short-period ground motions at home and abroad were selected in this paper, and their differences in time-history characteristics and response spectrum characteristics were compared and analyzed. The selected ground motions were input into a steel frame structure model, and through a nonlinear time-history analysis, the response differences of the steel frame structure under long- and short-period ground motions were studied. The results show that the average peak ground acceleration of short-period ground motions is 3.26 times that of long-period ground motions, and the average peak ground displacement is 10.89% lower than that of long-period ground motion. Under short-period ground motion, the average value of acceleration response at the top of the steel frame structure is 5.16 times that under long-period ground motion, and the average value of displacement response at the top of the structure is only 0.91% more than that under long-period ground motion. Under the action of long-period ground motion, the response of story drift ratio of the structure is larger, and the bottom of the structure is affected more widely. For high-rise steel frame structures in areas with long-period seismic hazards, long-period and short-period seismic hazards should be considered respectively. For medium- and long-period steel frame structures, it is suggested that the peak displacement should be selected as the seismic analysis index.