By breaking sensitive associations between attributes, database fragmentation can protect the privacy of outsourced data storage. Database fragmentation algorithms need prior knowledge of sensitive associations in the tackled database and set it as the optimization objective. Thus, the effectiveness of these algorithms is limited by prior knowledge. Inspired by the anonymity degree measurement in anonymity techniques such as k-anonymity, an anonymity-driven database fragmentation problem is defined in this paper. For this problem, a set-based adaptive distributed differential evolution (S-ADDE) algorithm is proposed. S-ADDE adopts an island model to maintain population diversity. Two set-based operators, i.e., set-based mutation and set-based crossover, are designed in which the continuous domain in the traditional differential evolution is transferred to the discrete domain in the anonymity-driven database fragmentation problem. Moreover, in the set-based mutation operator, each individual’s mutation strategy is adaptively selected according to the performance. The experimental results demonstrate that the proposed S-ADDE is significantly better than the compared approaches. The effectiveness of the proposed operators is verified.