The stainless steel core plate is an innovative lightweight structural material with broad application prospects. Experiments and finite element analyses were carried out to study the fire resistance of the stainless steel core plate beam in a three-sided fire. The load ratio and equivalent thermal resistance of the fireproof protective layer of stainless steel core plate beams were parametrically analyzed. A fire resistance design method for stainless steel core plate beams was presented. The results showed that the alternating sectional form of the core tube and mineral wool inside the beam resulted in an uneven temperature field distribution under a three-sided fire; with the premise that the weld was not damaged at high temperatures, the failure pattern of the core plate beam at high temperatures was the strength failure after the local instability of the web, which was the same as that at room temperature; the critical temperature of the lower flange decreased from approximately 870 °C to 485 °C, with an increase in the load ratio from 0.3 to 0.7; a prediction formula for the equivalent thermal resistance of fireproof protective layer required to reach a given fire resistance limit at different load ratios was established, which can be used for the design of stainless steel core plate beams for fire resistance.