Background and study aim: Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. AFP is the gold standard tumor marker for HCC, mean platelet volume (MPV) is a parameter obtained from complete blood count (CBC) by automated analyzers, shown to be increased in multiple malignancies and inflammatory conditions.This prospective study was designed to evaluate the diagnostic usefulness of MPV and MPV/ platelet count (PC) ratio in HCC patients due to chronic hepatitis C (CHC) infection. Materials and Methods: One hundred and twenty subjects enrolled in this study, they were divided into 4 equal groups: group I included 30 healthy subjects (control group), group II included 30 patients with chronic viral hepatitis without cirrhosis, group III included 30 cirrhotic patients without HCC and group IV included 30 cirrhotic patients with HCC.MPV, MPV/PC ratio & AFP were evaluated in all groups. Triphasic CT was done for patients of group IV to confirm the diagnosis of HCC. Liver biopsy was done for patients of group II to confirm the diagnosis of chronic hepatitis C. Results: MPV showed higher levels in HCC group compared to control, CHC, and cirrhotic groups with p value(<0.001) but there was no statistically significant difference between HCC group and cirrhotic group (p value=0.49), while MPV/platelet count ratio was higher in cirrhotic group (0.19±0.09 fL/ 109/L) than HCC group (0.14±0.08 fL/109/L) but also with no significant differences between both groups (p=0.06). There was insignificant positive correlation between MPV and AFP in HCC group ( Session [CurrentTestPartTermID];= 0.11 and p value =0.57). Also, there was insignificant negative correlation between MPV/PC and AFP in HCC group ( Session [CurrentTestPartTermID];= -0.17 and p value =0.37). In receiver operating characteristic (ROC) curve analysis, MPV had high sensitivity (73.33%), specificity (70 %), and area under curve (AUC) was 0.7, So it more better than MPV/platelet count ratio in diagnosis of HCC which had sensitivity (76.67%), low specificity (56.67%), and AUC was 0.63, while AFP had much higher sensitivity (90%), specificity (98.33%) than both studied parameters (MPV, MPV/PC ratio) with highly statistically difference when compared to MPV (p<0.001) and area under curve (AUC) was 0.9. Conclusion: MPV and MPV/PC ratio are less sensitive and specific than AFP in diagnosis of HCC. So AFP is still the gold standard marker in diagnosis of HCC and MPV and MPV/PC ratio may be used only in association with other markers like AFP to improve sensitivity of tumor detection.