Abstract: MoSe₂ spheres were prepared by a simple hydrothermal method using SiO₂ as template and as electrodes material, and applied as a sensing platform after electrodeposition of AuNPs on it. Hybridization chain reaction was used to amplify signal and HRP catalyzing H₂O₂+HQ system was used to produce electrochemical response for detection of microRNA-21. New method showed a good linear relationship ranging from 1.0×10^-16 to 1.0×10^-10 mol/L with a detection limit of 0.16 fmol/L (R_SN=3). The proposed biosensor was successfully applied for serum analysis.