The rGO/hemoglobin/CdS biocomposite (rGO/Hb/CdS) were prepared via a simple route. The water-soluble rGO/CdS composite was synthesized in aqueous solution with a facile hydrothermal route. CdS nanoparticles (NPs) were anchored uniformly on the graphene nanosheets. With L-cysteine (Cys) as the molecular linker, the Hb molecules were then adsorbed onto the CdS NPs to produce the rGO/Hb/CdS biocomposite NPs. The rGO/Hb/CdS was characterized employing UV-vis spectroscopy, powder X-ray diffraction (XRD), transmission electron microscopy (TEM) and field emission scanning electron microscopy (FE-SEM). The electrochemical behaviors of rGO/Hb/CdS were characterized with cyclic voltammetric technique (CV). A pair of well-defined and quasi-reversible cyclic voltammetric peaks was observed. The cyclic voltammogram demonstrated the direct electron transfer of the Fe(III)/Fe(II) couple of Hb. The glassy carbon electrode (GCE) modified with rGO/Hb/CdS displays an excellent electrocatalytic response to the reduction of H2O2 with a detection limit of 6 × 10−7 M (S/N = 3). A linear calibration curve can be observed in the range of 1.9 × 10−6 ∼ 1.5 × 10−4 M.