Abstract Background: Cancer associated fibroblasts (CAFs) are main components of tumor microenvirnoment. They act an essential role in tumor progression, invasion and unresponsiveness to chemotherapy. Aim of Study: This work aims to study the relation of CAFs with hepatocellular carcinoma (HCC) developement and progression. Material and Methods: This is an uncontrolled retrospective study carried upon 30 cases of HCC. Cases were collected from archives of Pathology Department and Early Cancer Detection Unit (ECDU), Faculty of Medicine, Benha University, and from International Medical Center during the years 2010-2015. Podoplanin (D2-40), alpha smooth muscle actin (α -SMA) and CD31 immunohistochemichal staining were performed and evaluated for each case. Results: Both D2-40 and α -SMA showed different distributions and levels of expression. D2-40 positivity was localized to the peri-tumoral area, while α -SMA was detected in both intra- and peritumoral areas. Expression of both markers was not statistically related to each other ( p >0.05). D2-40 was positive in 73.3% of casesand α -SMA showed high expressionin 60% of cases. Both positive D2-40 and high α-SMA showed positive relations to tumor grade (p