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Injection attack is still a serious form of threat to system security. This paper presents an instruction randomization technique based on compilation to effectively prevent code injection attacks. We analyze instruction format and create rules to replace or recover instructions. During compilation, our methods transform instructions according to the random replacement rules and generate the protected target programs. When executing, the protected program is recovered on a runtime code manipulation system in accordance with recovery rules. Results show that our method can correctly capture instructions and effectively thwart injection attacks while introducing an extra runtime overhead of 33% on average compared with execution without protection on the runtime code manipulation system.