In order to ensure quality of highway alignment design, and reasonably evaluate the design proposal, the main factors which affect the highway alignment design, including horizontal alignment design, vertical section design and combination of horizontal and vertical design, are analyzed. Based on these key factors, a system of evaluation based on game theory is constructed and the evaluation index is normalized from both qualitative and quantitative view. So an evaluation model of highway alignment design is established. Under the situation of highway alignment designs, the model and fuzzy comprehensive evaluation method are applied to determine the most suitable alignment design for that city. The best choice, design 3rd, is identical, but the sort of design 2nd and design 4th is not consistent with each other for the reason of large deviation of weight of the fuzzy comprehensive evaluation method. Because the evaluation model based on game theory can better determine the optimal weight, the evaluation is more reliable and it meets the practice. The results show that the model is effective and reliable.