<p>Aiming at the problem for inferior unmanned surface vehicle (USV) safely reaching complex target region, a novel defense penetration strategy is proposed based on the reach-avoid game. Firstly, a penetration condition is proposed through designing Nash equilibrium guidance law for USV to reach the penetration point which is determined by the joint security region and target region boundary. Secondly, the corresponding defense penetration strategy with two stages is proposed according to the non-penetration angle case (NPC) and penetration angle case (PAC). The penetrative USV can be converted to PAC under the strategy of NPC, and then move toward the penetration point according to the strategy of PAC. Moreover, the defense penetration strategy is proved by differential geometry theory, and two yaw velocity constraints are obtained. Finally, the effectiveness of the proposed defense penetration strategy is validated through simulation experiments, and its superiority under various scenarios is further corroborated via Monte Carlo simulation.</p>