The compact structure and stable performance of regenerative blowers at small flow rates render them attractive for the development of hydrogen recirculation devices for fuel cells. However, its optimization of structural parameters has not been yet reported in the literature. Along these lines, in this work, a mechanistic study was carried out in terms of examining the role of the flow channel structure on the performance of a regenerative-type hydrogen recirculation blower for the fabrication of automotive fuel cells. A three-dimensional computational fluid dynamics (CFDs) model of the regenerative blower was established, and the accuracy of the proposed model was verified through experimental data. The impact of structural parameter interactions on the performance of the regenerative blower was investigated using CFD technology, response surface methodology (RSM), and genetic algorithm (GA). First, the range of the structural parameters was selected according to the actual operation, and the influence of a single geometric factor on the efficiency was thoroughly investigated using CFD simulation. Then, a second-order regression model was successfully established using RSM. The response surface model was solved using GA to obtain the optimized geometric parameters and the reliability of the GA optimization was verified by performing CFD simulations. From our analysis, it was demonstrated that the interaction of the blade angle and impeller inner diameter has a significant impact on efficiency. The entropy generation analysis showed also that the internal flow loss of the optimized regenerative blower was significantly reduced, and the design point efficiency reached 51.7%, which was significantly improved. Our work provides a novel solution for the design of a recirculation blower and offers a reference for the optimization of regenerative-type hydrogen blowers.