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In this work, we reported a sensitive, label-free electrochemical biosensor based on the intrinsic topological insulator (TI) BiSbTeSe 2 for potential application in the determination of the HIV gene. With strong spin-obit coupling, TIs could have robust surface states with low electronic noise, which might be beneficial for the stable and sensitive electron transport between the electrode and electrolyte interface. Under optimized conditions of the biosensors using BiSbTeSe 2 , the differential pulse voltammetry (DPV) peak currents showed a linear relationship with the logarithm of target DNA concentrations ranging from 1.0 × 10 -13 to 1.0 × 10 -7 M, with a detection limit of 1.07 × 10 -15 M. The sensing assay also displayed good selectivity and stability after storage at 4 °C for 7 days. This work provides an effective way to develop biosensors with topological materials, which have a potential application in the clinical determination and monitoring field.