The purpose of this study is to examine the applicability of an infared spectroscopic methodology for the study of an environmental problem. The effect of cyanide concentrations on the biophysical conformation of the fish liver homogenate was determined by using an attenuated total reflectance (ATR)/Fourier transform infrared (FT-IR) microspectroscopy. Alive male model fish, Tilapia Zillii, was used. The liver from fish was isolated and homogenized in pH 8.0 Tris buffer solution. The results indicate that the IR peak intensity increased markedly in the C-H stretching range (3000-2800 cm-1), ester C = O stretching of lipids (1743 cm-1) and carbohydrate bands (1195-950 cm-1), but decreased in the amide I at 1649 cm-1 and the free asymmetric stretching band of phosphate at 1261 cm-1 with the increase of KCN concentrations. The marked release of hepatic enzymes and glutathione into homogenate induced by cyanide might account for the higher IR spectral peak intensity of fish liver tissue after treatment with KCN. The cyanide was also found to induce the protein structure of fish liver homogenate from alpha-helical conformation to beta-conformation.