Fire resistance and seismic performance are the two of the most important considerations for the design of construction steel. The fire resistance of the high strength construction steel, Q460FRE, which contains low Mo, was investigated by means of creep test under different experiment conditions. Then, the seismic performance of the Q460FRE steel, after being subjected to various fire temperatures, was characterized by internal friction analysis. The Q460FRE steel exhibited excellent fire resistance, and the yield strength at 600 °C was 67.4% of the yield strength at room temperature. The constitutive equation of creep stress and fracture time at 600 °C was established. The bearing tensile stress of the Q460FRE steel should be lower than 337 MPa to ensure at least 1 hour to evacuate from the fire. The creep stress and alternating temperature significantly affected the serration behavior of the creep strain. The internal friction analysis indicated that the seismic performance of the Q460FRE steel decreased with the increase in fire temperature, being consistent with the analysis results of the seismic performance characterized by the yield ratio.