This study aims to solve the overall lifting difficulty of mid-span steel box girders in steel-concrete hybrid continuous box girder bridges with variable sections under special environments, providing guidance for the design and construction control of such bridges. By analyzing the external measures adopted by different construction methods and their influence on the bridge-building state of the structure, theoretical research and real bridge calculations were conducted on the key influencing factors and control points of the sub-segment cantilever assembly method. The results indicate that the effect of temporary load and temporary external prestressing cannot be offset after the system transformation, and will affect the bridge-building state of the structure. Additionally, it is found that by conducting construction measures, the sub-segment cantilever assembly method can achieve the bridge-building state corresponding to the overall lifting method, and the efficiency of adjusting closure state by adopting upper external prestressing is 2.4 times that of adopting the lower external prestressing and can substantially reduce axial force on steel girders. Furthermore, in the sub-segment cantilever assembly method, crane weight has a greater influence on internal forces than the overall lifting method. Based on this, a process-oriented design method considering construction processes was developed for this type of bridge, and a key technology of designing temporary hinged devices at the closure was proposed, which can eliminate the adverse influence of bridge deck cranes on the bending moment at the steel girder root.