2-p-Toluidinynaphthalene-6-sulfonate (TNS) was discovered to perturb native fold of CopC protein and to induce loss of biological activity to some extent which was dependent on TNS concentration. Hydrophobic and electrostatic interactions were revealed to account for the perturbation by comparison with some analogy. TNS, with far low concentration of 10 −5 to 10 −4 M, is presented as a denaturant. So TNS should be deliberated in detecting macromolecular conformation change as single evidence at higher concentration.