Magnetic core gold shell nanostructures which integrate both SERS activity and superparamagnetism are widely utilized in SERS-based detection as SERS substrates, sample separation and preconcentration operators, as well as external magnetic field controlled directional carrier. However, most of the reported gold shells coated on the magnetic cores had smooth surfaces rather than branched nanostructures with enhanced SERS activity. Here, a novel type of Fe3O4-Au core-shell nanoparticles with branched gold shell was prepared by a seed-mediated method together with the shape induction agent AgNO3, and their growth process and mechanism, properties, as well as morphologically controlled synthesis were also investigated. The branched gold coated magnetic nanoparticles (B-GMNPs) with improved SERS performance were further utilized to build superparamagnetic and SERS-active capturers by assembling tetrahedral DNA onto their surfaces for sandwich-structured detection of cancer-related biomarker miRNA-21. The experimental results indicate that highly sensitive and specific detections can be obtained by the proposed SERS sensing system including B-GMNPs and tetrahedral DNA, and the limit of detection (LOD) of miRNA-21 in serum is 623 amol L −1 . These B-GMNPs can be used as good SERS substrates with the functions of external magnetic field controlled sample separation and directional enrichment for effective SERS-based biochemical sensing and detections.