Owing to its promising biocompatibility and reliable sensitivity, semiconductor-guided surface-enhanced Raman scattering (SERS) technology has aroused widespread concern in clinical immunoassays. Herein, the well-improved light capture capability of MoS2 with a novel three-dimensional (3D) flower-like morphology was combined with the synergistic chemical enhancement from a MoS2@red phosphorus (RP) hybrid system, facilitating an attractive non-metallic SERS-based detection of ferritin in serum. Owing to the remarkable enhancement factors of both the immunoprobe and immunosubstrate, which were comparable to noble metal, an extremely low limit detection of 11.5 pg mL-1 was achieved in the absence of fluorescence interference. In particular, the trace ferritin in the clinical serum sample was successfully monitored, demonstrating superior sensitivity to the traditional chemiluminescent method. Overall, this study convincingly revealed the feasibility and reliability of SERS-based immunoassays induced by biocompatible semiconductors, which has opened a new way to implement the detection and tracking of biomarkers in the human body.