This study aims to analyze the effect of high-altitude environment on drivers’ mental workload (MW), situation awareness (SA), and driving behaviour (DB), and to explore the relationship among those driving performances. Based on a survey, the data of 356 lowlanders engaging in driving activities at Tibetan Plateau (high-altitude group) and 341 lowlanders engaging in driving activities at low altitudes (low-altitude group) were compared and analyzed. The results suggest that the differences between the two groups are noteworthy. Mental workload of high-altitude group is significantly higher than that of low-altitude group, and their situation awareness is lower significantly. The possibility of risky driving behaviours for high-altitude group, especially aggressive violations, is higher. For the high-altitude group, the increase of mental workload can lead to an increase on aggressive violations, and the situation understanding plays a full mediating effect between mental workload and aggressive violations. Measures aiming at the improvement of situation awareness and the reduction of mental workload can effectively reduce the driving risk from high-altitude environment for lowlanders.