Abstract: In order to study the effects of uneven adhesion coefficient and crosswind on alignment design indexes, a six-axle semi-trailer is selected as the typical vehicle model to investigate the effects of uneven adhesion coefficient caused by superelevation under the condition of rainfall on the truck's lateral stability, quantifying the crosswind using TruckSim. Based on the basic theory of vehicle dynamics, vehicle safety driving model is established. Also, the minimum radius is calculated with the consideration of uneven adhesion coefficient and crosswind. The results show that the effects of uneven adhesion coefficient and crosswind on the truck's lateral stability increase with the increasing of the truck's speed. Truck's lateral slide instability begins to appear when crosswind grade grows up to 9 or above. According to sensitive analysis, speed, rainfall, crosswind, and the interaction of the speed and rainfall have significant influences on the truck's lateral stability. The results quantify the effects of uneven adhesion coefficient and crosswind on truck's lateral stability. The advised index for horizontal curve design control is proposed, which provides a good reference for road safety design and safety protective measures. It can also provide theoretical basis and guidelines for highway safe operation in the windy and rainy areas.