this study was to define markers of cirrhosis and HCC using SR-FTIR microspectroscopy. Methods: The study has been focused on liver samples obtained from surgical specimens including normal livers (n = 7) and patients with HCC on cirrhosis from alcohol (n = 6) or HCV (n =6) aetiology. Frozen tissue sections stained with H&E were performed for histological examination. Adjacent tissue sections were investigated using SR-FTIR microspectroscopy experiments. The variance was addressed by multivariate statistical methods such as principal component analysis (PCA). Results: We strived firstly to discriminate the spectroscopic profile of healthy and pathological liver. The infrared spectral pattern of cirrhosis or HCC exhibited significant differences in the composition of lipids, proteins and sugars when compared with tissue from normal liver. Then, we investigated the spectral differences that discriminate tumor tissue from cirrhosis. Detailed analysis demonstrates a frequency shift in proteins suggesting changes in the proteome but the major discrimination was observed on sugars. Furthermore, SR-FTIR experiments followed by PCA analysis allowed the discrimination between hyperplastic and dysplastic cirrhotic nodules on sugars. Infrared signatures of dysplastic nodules superimposed with HCC suggesting that FTIR microspectroscopy allows diagnosing tissue changes associated with early stages of cancer. Finally, experiments were performed on a conventional IR microscope using an internal IR source. Despite the lower spatial resolution of such a device, it was possible to reproduce the results obtained in the exploratory phase using synchrotron radiations. Conclusions: Infrared microspectroscopy allows discriminating various grades of cirrhosis and HCC. This approach that can be easily implemented into hospitals may open new avenues for clinical applications and personalized medicine.