Background: In the entire world, hepatocellular carcinoma (HCC) is considered as one of the most prevalent cancers. For earlier identification to enhance the clinical outcomes of HCC patients, more sensitive and specific indicators are required. Aim: To identify HCC, it is necessary to assess the annexin A2 levels in both compensated and decompensated HCV-treated patients. Methods: At the time of diagnosis and before starting treatment, blood specimens from 40 HCC individuals were taken and isolated plasma specimens were maintained at -80 °C until ANXA2 assays. The human ANXA2 enzyme-linked immunosorbent test (ELISA) kit was used to collect blood specimens from forty individuals with CHC but no HCC at the same duration as the blood specimens from HCC patients. Anti-ANXA2 antibodies were utilized as identification antibodies. Results: With a p-value of <0.001, the ANXA2 level sensitivity and specificity test demonstrated a statistically significant difference in the identification of HCC cases in both compensated and decompensate populations. In comparison to the decompensated group, the ANXA2 level's sensitivity in diagnosing HCC patients was 90% in the compensated status. Regarding AFP and ANXA2 levels, there was a statistically significant distinction (p <0.001) between the two study groups, with a greater mean among the HCC group. Conclusion: The combination of annexin A2 and AFP significantly boosts the diagnostic capability of this promising HCC diagnostic marker. Its serum concentration can be used as an effective, non-invasive tumour marker for HCC identification.