Abstract: Net-like molybdenum selenide was prepared by a hydrothermal method. A novel DNA electrochemical sensor was fabricated by modifying molybdenum selenide and Au nanoparticles on glassy carbon electrode and coupled with hybridization chain reaction for ultrasensitive determination of specific DNA sequences. The molybdenum selenide nanosheets have good electro-conductivity and large specific surface area, which can amplify the detection signal when couple with hybridization chain reaction. For DNA detection, the linear range of the developed assay was 1.0×10-10 ~1.0×10-14 mol/L with a low detection limit of 8.0×10-15 mol/L (S/N=3). This sensor showed a good specificity for the target DNA detection, with the capability to discriminate single-base-pair mismatched DNA mutation and three-base-pair mismatched DNA mutation.