Abstract: This paper mainly studies the application effects of calcium sulfate whisker, a new kind of high-modulus and inorganic-modified material in asphalt mixture. According to the Marshall test, this research designs the ratio of the mixed material, so as to determine the mixed quantity of calcium sulfate whisker. Based on the related studies about road performance, it makes a comparative study among these three mixed materials. The results indicate that the high-modulus asphalt mixture with modified calcium sulfate whisker can effectively improve the mixed materials’ stability in high temperature, water stability and anti-fatigue performance; meanwhile, it doesn’t decrease their performance in low temperature. Therefore, it is helpful to solve the common problems in highway engineering, such as rutting, water damage and so on. The feasibility analysis proves that the application of high-modulus asphalt mixture with modified calcium sulfate whisker could achieve greater economic and social benefits while ensuring the good road performance of the road.