In investigating guanidine hydrochloride (GuHCl) denatured chlorophylls using the terahertz time-domain spectroscopy, the authors explored the feasibility and sensitivity of the terahertz technology in sensing protein denaturation and associated conformation changes. It was found that the conformation change was induced by the C=O group of chlorophyll, interacting with the N-H group of GuHCl to form hydrogen bonds, which shows higher absorption than the native ones and an absorption peak around 1.7 THz in our THz spectra. The results presented here demonstrate that THz-TDS has both advantages and disadvantages in monitoring denaturation process of proteins, which is important in applying THz-TDS technique to the study of biomolecules.