Tetracycline (TC), as a high-world consumption antibiotic, has a stable molecular structure and low biodegradability, which makes it highly demanding to be removed. Herein, we propose a viable solvothermal strategy for the synthesis of flower-like NiSe-Fe3O4/C S-scheme heterostructure from the hierarchical Ni/Fe-MOF sacrificial template and its application to the photocatalytic degradation of TC in a designed spiral shape microfluidic photoreactor. The electrochemical, optical, microscopic, density functional theory (DFT) calculations, and experimental results, have thoroughly confirmed that coupling of the NiSe-Fe3O4 heterostructure and carbon sheath can promote superior light-harvesting ability and photoexcited charge separation and transfer efficiency, resulting in robust photocatalytic performance. The photocatalytic degradation efficiency of TC was reached more than 85% in 15 min by NiSe-Fe3O4/C. Moreover, detailed mechanism evaluation admits the crucial effect of the produced reactive oxygen species (radical dotOH and radical dotO2−) leads to significant performance. This work provides new insight into the rational design of bi-MOF-derived S-scheme heterostructure with an internal electric field that derives charge separation and transfer. In addition, the rate of mass transfer in photocatalytic reaction is facilitated by proposing microfluidic systems as a capable process and intensification strategy toward environmental remediation applications.