Background/Aim: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for approximately 782,000 new cancer cases and 745,000 deaths worldwide. Because HCC is usually detected at an advanced stage, the prognosis is worse. As a result, early diagnosis and biomarker discovery may greatly enhance results. Material/Methods: In a recent study, the study population include 173 patients (130 males and 43 females, aged 28-71 yrs.), with different degrees of liver fibrosis and 52 patients with HCC. According to the METAVIR scoring system, non-significant fibrosis (F0-F1) was identified in 33 patients (F0 in 22 and F1 in 11 patients), and significant fibrosis (F2-F4) was identified in 88 patients (F2 in 21, F3 in 23, F4 in 44 patients). Serum samples of 173 patients were tested for Cartilage oligomeric matrix protein (COMP) levels using ELISA. Statistical analysis was performed using SPSS. Results: The result revealed that there was very highly significant increase (p< 0.0001) in ALT, AST, and ALP in group F4 compared to group F0-F1 and F2-F3 but the conc. of AFP (mean = 217.12 ng/ml) very highly significant in HCC compared to F0-F1, F2-F3 and F4. It was discovered that HCC patients' serum levels of COMP (mean = 19.69 pg/mL) were significantly higher (p < 0.0001) than in the significant liver fibrosis patients (F2, F3) (mean = 8.83 pg/mL), non-significant liver fibrosis (F0-F1) control group (mean=3.35 pg/mL) and cirrhotic liver patients (F4) (mean = 13.82 pg/mL). Conclusion: The HCC-COMP biomarker test offers a very precise diagnostic approach for the identification of HCC.