We used functional near-infrared spectroscopy (NIRS) to investigate the role of the prefrontal cortex (PFC) on unexpected events during simulated driving. The subjects were instructed to respond to a verbal turning-command and to change the driving route immediately (Route-change condition). Compared with the baseline condition (Route-fixed condition), subjects showed greater oxy-hemoglobin concentrations in their left prefrontal cortex. And the first experimental trial under Route-change condition showed greater oxy-hemoglobin concentrations in the left and right hemispheres. The results imply that PFC is involved in unexpected events and the first time of salience stimulus has the most significant effect on PFC.