Background: Hepatocellular carcinoma is the most common liver tumor, which is the fifth most prevalent cancer overall. Objective: The comparison of alpha-fetoprotein (AFP) and serum vitronectin (VTN) in the diagnosis and prognosis of hepatocellular carcinoma in addition to hepatitis CV-related liver disorders. Patients and Methods: There were 60 participants in this prospective observational study, and they were split into 4 groups as follows: Group 1 had ten average people. Ten individuals in group 2 with hepatitis C virus infection were included. Twenty individuals with cirrhosis were in group 3. Twenty patients in Group 4 with HCC (in addition to cirrhosis caused by the hepatitis C virus) had tests for vitronectin and AFP before and three months after intervention. Results: We discovered a statistically significant difference in low platelet count, high serum Cr, high INR, low serum Alb high bilirubin, and greater aspartate aminotransferase between the cirrhotic group and the non-cirrhotic groups. The median level of alfa-fetoprotein in group 4 (Hepatocellular carcinoma patients) was 110 IU/millilitre, which was substantially higher than the median value in the other research groups. The median vitronectin level was unable to differentiate among the different research groups. There was no statistically significant difference in the serum level of vitronectin between the 3 categories in group 3 (cirrhotic patients), according to the Child's classification. Conclusions: Chronic HCV infection and hepatocellular carcinoma are both health issues in Egypt. As blood AFP levels may be normal in as much as forty percent of patients with hepatocellular carcinoma, particularly in the early stages, it has low specificity for recognising cirrhosis, chronic hepatitis, or cholangiocarcinoma and limited sensitivity for detecting hepatocellular carcinoma.