Research on the human pathogen Mycobacterium tuberculosis XL Twin Mattress (Mtb) would benefit from novel tools for regulated gene expression.Here we describe the characterization and application of a synthetic riboswitch-based system, which comprises a mycobacterial promoter for transcriptional control and a riboswitch for translational control.The system was used to induce and repress heterologous protein overexpression reversibly, to create a conditional gene knockdown, and to control gene expression in a macrophage infection model.Unlike existing systems for controlling gene expression in Mtb, the riboswitch does not require the co-expression of any accessory proteins: all of the regulatory machinery is encoded by a 5mm short DNA segment directly upstream of the target gene.The inducible riboswitch platform has the potential to be a powerful general strategy for creating customized gene regulation systems in Mtb.