Background: Hepatocellular carcinoma (HCC) is the third most common cause of death from cancer worldwide which accounts for 80%-90% of primary liver cancer. It is characterized by a very poor prognosis. Outcome of HCC depends mainly on its early diagnosis. Serum α-fetoprotein (AFP) is the marker that has been widely used for screening and diagnosis of HCCs. However, development of false-negative or false-positive rates with (AFP) was as high as 30%-40% for patients with small HCCs. Insulin resistance (IR) is found to occur early in the course of Hepatitis C  (HCV) infection, independent of BMI (body mass index), stage of liver disease and presence or absence of diabetes. Recently, it has been observed the synergistic effect of IR and viral hepatitis in HCC development among HCV infected patients. Therefore, this study was done to investigate the correlation between HOMA-IR and HCC patients. Methods: Clinical and biochemical characteristics were investigated for 50 HCC patients related HCV and 50 normal controls. HCC patients were diagnosed by ultrasound assessment, abdominal triphasic CT and serum AFP. Homeostasis model assessment of IR (HOMA-IR) was investigated to all 100 participants. Results: Obese patients in HCC group showed significantly higher frequency of high HOMA-IR when compared to non- obese patients (P=0.001). HOMA-IR value increases as tumor size of HCC increases. Conclusion:  Hepatocarcinogenisis may result from a combination of this direct viral effect and the influence of an array of metabolic factors resulting from virus-induced insulin resistance