Tabriz University of Medical Sciences BioImpacts 2228-5652 15 1 2025 01 19 Potential role of epidermal growth factor receptors (EGFR) signaling in the pathogenesis and management of hepatocellular carcinoma 30905 30905 10.34172/bi.30905 EN Samah Saleh Ahmed Al-Awadhi https://orcid.org/0009-0001-4102-0652 Prakash Patil Praveenkumar Shetty Padma K Shetty Reshma A Shetty Vijith V Shetty https://orcid.org/0000-0002-0628-5831 Journal Article 10.34172/bi.30905 2024 12 06 2025 01 21 Hepatocellular carcinoma (HCC) is the most prevalent type of primary liver cancer, accounting for roughly 90% of all liver malignancies worldwide, and remains the leading cause of cancer death worldwide. Cirrhosis, viral hepatitis, non-alcoholic fatty liver disease (NAFLD), or liver injuries caused by alcohol are all chronic diseases that have a close association with the pathogenesis of HCC. A key factor in the progression of these diseases to HCC is the activation of the epidermal growth factor receptor (EGFR) signalling pathway. The ErbB family of receptor tyrosine kinases, which includes EGFR, is essential for inflammation, cell division, and liver regeneration. In HCC, EGFR expression and hyperactivation are closely associated with tumor growth, metastasis, and patient prognosis. This review explores the structural and functional aspects of EGFR, its signalling mechanisms in hepatocellular proliferation and apoptosis, its role in liver fibrosis, and the transition from chronic liver injury to advanced HCC. Moreover, crosstalk between EGFR-mediated pathways and other signalling pathways, such as PI3K/AKT/mTOR and MAPK/ERK, contributes to resistance to targeted therapies, suggesting that molecular regulation needs to be improved in strategies targeting EGFR and its downstream pathways.