<p>Alleviating the cross-regulation (CR) problem is one of the hottest research topics in single-inductor multiple-output (SIMO) dc-dc converters. However, the theoretical optimal CR has not been determined. To fill this gap, this paper quantitatively analyzes the CR optimization limit for SIMO boost converter with a differential evolution (DE) algorithm. First, a mathematical model of the puzzle is established, which is essentially a combinatorial optimization problem with a nonlinear objective function and constraints. This multi-dimensional problem is too complex to solve directly. Hence, the differential evolution (DE) algorithm is employed to heuristically search out a set of free duty cycles of switches to attain a minimal CR. In addition, the proposed method is capable of conveniently seeking the optimal CR with various requirements, including different output priority, constrained maximum inductor current, and different transient processes, which is beneficial to comprehensively acknowledge the dynamic performance of SIMO converters and guide the controller design in engineering applications. Finally, the effectiveness of proposed method is experimentally verified.</p>