High-order sideband nonlinear optical properties in a DNA–quantum dot coupled system are investigated theoretically here. In this paper, we demonstrate the significant enhancement of the third- and fifth-order optical nonlinear properties of the system by applying the pump-probe technique with pump-exciton detuning tuned to zero. It is shown clearly that these phenomena cannot occur without the DNA–quantum dot coupling, implying some potential applications like DNA detection. We can also obtain and tune the significantly amplified sideband beams at frequencies ωp
2ωD. This research could provide people a deeper insight into the nonlinear optical behaviors in coupled DNA–quantum dot systems.