BACKGROUND Hepatocellular carcinoma is one of the most common malignant tumors worldwide. Currently, the most accurate diagnosis imaging modality for hepatocellular carcinoma is enhanced magnetic resonance imaging. However, it is still difficult to distinguish cirrhosis lesions, and novel diagnosis modalities are still needed. AIM To investigate the feasibility of hyperspectral analysis for discrimination of rabbit liver VX2 tumor. METHODS In this study, a rabbit liver VX2 tumor model was established. After laparotomy, under direct view, VX2 tumor tissue and normal liver tissue were subjected to hyperspectral analysis. RESULTS The spectral signature of the liver tumor was clearly distinguishable from that of the normal tissue, simply from the original spectral curves. Specifically, two absorption peaks at 600-900 nm wavelength in normal tissue disappeared but a new reflection peak appeared in the tumor. The average optical reflection at the whole waveband of 400-1800 nm in liver tumor was higher than that of the normal tissue. CONCLUSION Hyperspectral analysis can differentiate rabbit VX2 tumors. Further research will continue to perform hyperspectral imaging to obtain more information for differentiation of liver cancer from normal tissue.