To better understand the effect of multiple factors on terrain design for the airport runway, the semi-automatic runway topography optimization (SRTO) was proposed based on the differential evolution (DE) algorithm. The longitudinal profile was simulated, and the results were applied in GS (Gongshan, a city located southwest of China) airport. Moreover, we present analysis of the number of slope changing point, cross slope direction and weight coefficient to optimize the components of the algorithm. the operation iteration speed of the program can be optimized up to less than 1 second per scheme by a practical algorithm structure design. The result showed that the number of slope changing point in longitudinal is the most significant factor for earthwork decline. A widely optional range of cross slopes decreases the excavation volume near the hillside. The weight coefficient can keep the total volume (filling and excavation) change in an accepted range while decreasing the real volume(difference of filling and excavation). Moreover, the real volume can be declined to -0.29 10 4m 3, and the total volume only increased 120.03 10 4m 3. The findings of this paper could optimize the earthwork for runway design when a target influenced by multiple constraints.