In order to study the terminal precision guidance of the hypersonic air-to-surface missile with constraints, the guidance law was designed respectively in the pitching plane and swerve plane. After the constraints of miss-distance, impact angular and orientation angular were considered synthetically, and the three-dimensional optimal variable structure guidance law was derived from the optimal control. Moreover, the traditional algorithm of max-velocity control was also mended by the adaptive gradient method and Takagi-Sugeno fuzzy system. Through the simulation test of the characteristic trajectory, the optimal variable structure guidance law with constraints is not only satisfied with the precision guidance in the multi-constraint conditions, but also has excellent trajectory in terminal guidance.