Background: Mean platelet volume (MPV) is a parameter routinely provided by the automated blood analyzers. In the last few years, MPV and MPV/platelet count (PLT) ratio were investigated in some medical conditions such as sepsis, myocardial infarction, pulmonary embolism and lung cancer. Objective: This work aimed to study the significance of MPV and MPV/PLT ratio in chronic hepatitis C patients with hepatocellular carcinoma (HCC). Patients and Methods: Mean platelet volume and MPV/PLT ratio were determined in 60 patients with chronic hepatitis C virus (HCV) infection divided into 3 groups: patients with chronic hepatitis, patients with cirrhosis and patients with HCC as well as 10 healthy subjects were included as control. Results: Mean platelet volume significantly increased in HCC group compared to control group, patients with chronic hepatitis and patients with cirrhosis. Mean platelet volume/platelet count ratio significantly increased in HCC group compared to control group and patients with chronic hepatitis only. In receiver operating characteristic (ROC) curve analysis, a cut-off point of 10.5 fl of MPV was found to be 100% sensitive and 55% specific for detection of HCC (the specificity rose to 92.5% when combined to alpha feto protein (AFP)), a cut-off point of 0.05 (fl/(10³/ul)) of MPV/ PLT ratio was found to be 100% sensitive, and 47.5% specific for detection of HCC (the specificity rose to 92.5% when combined to AFP). Conclusion: Mean platelet volume and MPV/PLT ratio are independent or adjunctive, easy and cheap markers that may be used in detection of HCC in patients with HCV infection.