Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer worldwide, and the third most frequent oncological cause of death. Being detected at an advanced, non-resectable stage, HCC is associated with a low 5-year survival and poor prognosis. Recently some studies have demonstrated that the prognosis of HCC correlates to various molecular markers. In this view, we have studied here the immunohistochemical reactivity of 15 HCC cases diagnosed in the last three years for some biomarkers with prognostic value such as p53, alpha-fetoprotein (AFP) and CXCR4, in correlation with the major clinicopathological parameters of these patients. In our casuistry the most prevalent architectural pattern was the trabecular (53.4%), followed by the pseudoglandular pattern (20%), while the less common diagnosed were the solid and pleomorphic variants. More than 80% of these tumors were well to moderate differentiated; developed in the six decade, twice more common in men and diagnosed in advance stages (80% of cases in stages ≥III). Markers such as CK18, CK7 and CEA were usefully in order to certify the primary liver origin and the hepatocellular differentiation of these tumors. Moreover, biomarkers as p53, AFP and CXCR4 were positive especially in more advance stages suggesting the possibility of their utilization as prognostic factors and in the therapeutically stratification of such patients.