Abstract: Current consideration of smoke toxicity during a fire in the design of railway tunnel evacuation and rescue has been mainly focused on plain areas. However, with the increase in altitude, the oxygen concentration in the tunnel decreases, aggravating the toxic gases in the smoke of the fire, especially CO toxicity, and reducing the tolerance time of trapped personnel for identical CO concentration. Therefore, it calls for more discussions and investigations on the safety of the design according to the control standards for smoke CO concentration in fires in plain areas.With the help of the CFK formula, this paper, based on the two scenarios of casualty within 30 minutes, and loss of evacuation ability within 5 minutes, investigates the effect of altitude on the time of human tolerance of the same smoke CO concentration, as well as the limits of smoke CO concentration in tunnel fires at different altitudes. The results show that the increase in the altitude and in the smoke CO concentration both accelerates the changing rate of human COHb concentration during the rapid-growth phase. The time of human tolerance of the same smoke CO concentration gradually drops with the increase of altitude. This paper shows the prediction formula for the reduction factors of the time of human CO tolerance at different altitudes. With the value of human COHb concentration being less than 60% and 28.6% as the benchmark, this paper establishes the calculation formulas of human tolerance of critical smoke CO concentration for the two scenarios of casualty within 30 minutes and loss of evacuation ability within 5 minutes during fires at different altitudes, respectively.