Gene regulatory systems that offer reliable and predictable control over gene expression inmammalian cells have broad applications that include basic biological discovery and human gene therapy. Ligand-inducible bacterial repressor proteins are commonly used to regulate genes in mammalian hosts. The repressors can tune transcription through direct interaction with operator sequences placed within or around promoter elements. Furthermore, fusion of bacterial repressors to eukaryotic transcriptional activating or repressing domains can afford the associated inducible trans-acting behavior, with appropriate placement of operator sequences. While a variety of repressor systems have been adapted to work in various mammalian cell lines, these often suffer from high leakiness or inducer-mediated toxicity in the host cell, thus hampering applications. Here we describe the design and characterization of a salicylic acid (SA)-inducible gene expression system in (human) Jurkat cells. Noteworthy features of this gene expression system include the small size of the repressor/activator (10-16 kDa), use of an FDA-approved inducer (drug), and its demonstrated repression/de-repression activity a human T-cell line.