Since the 18th National Congress of the Communist Party of China, it has been proposed to strengthen cultural confidence, which originates from historical confidence. As historical relics, the value of cultural relics is self-evident, and the importance of cultural relic protection work is further strengthened. As a linear engineering project, expressways have the characteristics of long mileage and wide impact range. In survey and design, the expressways may have a certain impact on cultural relics along the route. Focusing on the design of expressway route selection and the protection of cultural relics, and combined with the analysis on the practical engineering cases, a concept of expressway route selection based on cultural relic protection is proposed, which provides the reference experience for similar projects.