Background <p>Hepatocellular carcinoma (HCC) represents a major global health burden, and early identification remains challenging because current diagnostic options have limited sensitivity. This study evaluated circulating CD90 + , CD133 + , and EpCAM + peripheral blood mononuclear cell (PBMC) populations in experimental liver fibrosis and HCC to determine their association with disease severity.</p> Methods <p>Male Wistar rats were randomly grouped into four groups: control, olive oil, fibrosis, and HCC. PBMCs isolated from peripheral blood were analyzed by flow cytometry to determine the percentages of CD90 + , CD133 + , and EpCAM + cells. Apoptosis-related markers, including caspase-3 and Annexin V; COX-2 expression; oxidative stress markers, including MDA and NO; liver function parameters, including ALB, GGT, and bilirubin; and the inflammatory cytokine IL-1β were also assessed. The prepared liver tissues were subjected to histopathological examination by H&amp;E and Masson’s trichrome stain.</p> Results <p>CD90 + , CD133 + , and EpCAM + PBMC percentages showed a graded increase across the experimental groups. All three markers were significantly elevated in the fibrosis group, indicating association with chronic liver injury and fibrogenic remodeling. CD133 and EpCAM increased further in the HCC group, whereas CD90 showed marked elevation in both fibrosis and HCC without clear discrimination between the two states. These markers were positively associated with several indices of disease severity, including caspase-3, COX-2, GGT, IL-1β, AFU, and histological fibrosis. Histopathological examination confirmed progressive architectural distortion, fibrosis, and neoplastic changes in the diseased groups.</p> Conclusion <p>Circulating CD90 + , CD133 + , and EpCAM + PBMC populations may serve as progression-associated candidate biomarkers in experimental liver disease. However, further validation in clinical studies is warranted to determine their efficacy and specificity in human patients.</p>