BACKGROUND: Hepatocellular carcinoma (HCC) is a highly incident malignancy with a dreadful prognosis. It evolves through a multistep process, with a contribution from different stromal cells like cancer associated fibroblasts. Podoplanin is a glycoprotein that influences epithelial mesenchymal interplay facilitating the tumor invasion. AIM: The aim of the study was to evaluate the immunohistochemical expression of Podoplanin in HCC in cancer associated fibroblasts (CAFs) and malignant hepatocytes as well as assessing the lymphovascular density, and correlating them with the clinicopathological parameters. METHODS: Sixty formalin-fixed paraffin-embedded HCC tissue blocks were retrieved from the pathology Department of the National Hepatology and Tropical Medicine Research Institute and Kasr Al-aini Hospital during the period of January 2012 till December 2019. The specimens were obtained through partial or total hepatectomy inclusion criteria included HCC cases obtained through resection type biopsy and those having no history of pre-operative cancer therapy, while cases with insufficient data, core biopsy, and marked necrosis were excluded from the study. Tumor tissue blocks were immunostained for Podoplanin and its expression was interpreted in lymphatic vessels, CAFs, and malignant hepatocytes. RESULTS: Podoplanin expression in CAFs and malignant hepatocytes was detected in the majority of HCC cases (81.7%) and (88.3%), respectively. The malignant hepatocytes showed increased expression of Grade 1 immunostaining (36.7%). High lymphovascular density was detected over the majority of the cases (73.3%). Podoplanin expression was significantly correlated with higher mean age, male gender, presence of viral infection, cirrhosis, and higher tumor grade. Unifocal tumor mass, tumor size <5 cm, and presence of invasion showed a significant correlation with Podoplanin in malignant hepatocytes and CAFs for the formers and the later, respectively. CONCLUSION: Podoplanin is highly expressed in HCC, which could be used as a prognostic marker for lymphangiogenesis. Furthermore, within the malignant hepatocytes and CAFs suggesting a role in hepatocellular tumorigenesis. Podoplanin targeted therapy can be investigated to slow down the tumor progression and metastasis.