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Recent active worm propagation events show that active worms can spread in an automated fashion and flood the Internet in a very short period of time. Our previous results show that P2P systems with large number of hosts can be a potential vehicle for the active worm attacker to achieve fast worm propagation in the Internet. In this paper, we propose a region-based active immunization defense strategy in P2P systems to fight against P2P-based active worm attacks. We develop an analytical approach to evaluate the efficiency of our proposed defense strategy. Our numerical analysis results show that: although P2P-based attacks can significantly improve the attack performance by attacking vulnerable P2P systems, our proposed defense strategy can effectively slow down the worm propagation. We also observe that defense parameters such as defense list size, worm detection success ratio, and immunization rate have significant impacts on the performance of our defense strategy.