Kaohsiung Cross-Harbor Tunnel connecting Kaohsiung City and Cijin District is designed to serve the needs of both container traffic of Kaohsiung Port and Cijin District residents. A serious fire accident in the tunnel will cause disruption to the operation of the tunnel and the impact will be enormous. Both ends of the tunnel have a U-shaped slope. Due to the proximity to the seaport, the wind direction of natural winds in the winter and summer seasons is obviously reversed by consulting local weather data. This study analyzed the impact of natural winds on the occurrence of fire accidents by using the internationally renowned fire simulation software - FDS. By simulating three tunnel fire scenarios under the influence of natural wind, the results show that the phenomenon of stack effect is obvious in this U-shaped tunnel. For example, the spread of smoke and hot gas in the fire are greatly affected by natural winds. The results of this study were not discussed in the past. The formulation of fire rescue strategy in the tunnel have to ake into consideration the effects of natural winds.