The missile confrontment technology was taken as the background. The mid-course evasive maneuver guidance strategy was studied based on the differential game theory. The ballistic missile used differential game guidance law as the evasive strategy, while the terminal guidance of Exo-atmospheric Kinetic Vehicle (EKV) was the proportional guidance law. Firstly, taking the miss-distance and the energy of both sides as the performance index, the optimal guidance law was deduced with its analytic expression came only with the starting time of maneuvering, the initial position and the velocity of both sides. Then the penetration effect of the ballistic missile is verified through missile confrontment simulation. The results of the simulation show that with the limited acceleration, selecting the properly and timely maneuvering can greatly reduce the interception effect of EKV.