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The attribute reduction and rule generation (the attribute value reduction) are two main processes for knowledge acquisition. A self-optimizing approach based on a difference comparison table for knowledge acquisition aimed at the above processes was proposed. In the attribute reduction process, the conventional logic computation was transferred to a matrix computation along with some added thoughts on the evolution computation used to construct the self-adaptive optimizing algorithm. In addition, some sub-algorithms and proofs were presented in detail. In the rule generation process, the orderly attribute value reduction algorithm (OAVRA), which simplified the complexity of rule knowledge, was presented. The approach provided an effective and efficient method for knowledge acquisition that was supported by the experimentation.