FT-IR spectroscopy is a vibrational spectroscopic technique that can be used to investigate the biochemical changes at the molecular level in various tissue transformation conditions [hyperplasia, dysplasia and well differentiated squamous cell carcinoma (WDSCC)] with respect to control tissues in DMBA-induced hamster oral carcinogenesis. The results revealed that a significant increase in the amount of proteins and nucleic acid contents and a decrease in the amount of lipids contents are observed in WDSCC when compared to control, hyperplasia, dysplasias. In addition, the detailed secondary structure of proteins in the control and various tissue transformation conditions is also presented. Further, the diagnostic algorithms based on PC-LDA achieved an overall sensitivity of 80-100 % and specificity of 81-100 %. The present study further shows a great potential of FT-IR spectroscopy as a complimentary tool, which may provide a rapid screening method and have potential use in the diagnosis of dysplasia and early, non-invasive oral cancer. © 2021 Elsevier B.V., All rights reserved.