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Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver with elevated mortality. Experimental treatment with antioxidants has a beneficial effect on the experimental models of HCC. Arthrospira maxima (spirulina) and its phycocyanin have antitumoral action on different tumoral cells. However, it is unknown whether phycocyanin is the responsible molecule for the antitumoral effect on HCC. Photoacoustic spectroscopy (PAS) stands out among other spectroscopy techniques for its versatility of samples analyzed. This technique makes it possible to obtain the optical absorption spectrum of solid or liquid, dark or transparent samples. Previous studies report that assessing liver damage in rats produced by the modified resistant hepatocyte model (MRHM) is possible by analyzing their blood optical absorption spectrum. This study aimed to investigate, by PAS, the effect of phycocyanin obtained from spirulina on hepatic dysfunction. The optical absorption spectra analysis of the rat blood indicates the damage level induced by the MRHM group, being in concordance with the carried out biological conventional studies results, indicating an increase in the activity of hepatic enzymes, oxidative stress, Bax/Bcl2 ratio, cdk2, and AKT2 expression results, with a reduction in p53 expression. Also, PAS results suggest that phycocyanin decreases induced damage, due to the prevention of the Bax, AKT2, and p53 altered expression and the tumor progression in a HCC rat model., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential no conflicts of interest with respect to the research, authorship, and/or publication of this article: The researchers are fellows of EDI, COFAA, and SNI.