Hepatocellular carcinoma (HCC), one of the most lethal tumors globally, has long been a research hotspot due to its complex pathogenesis involving interactions between genetics, metabolism, and viral infections. Recently, at the 2025 EASL Liver Cancer Summit held in Paris, France, a study by Professor Mohamed Abdel Samie's team from the Department of Hepatology and Gastroenterology at the National Liver Institute, Menoufia University, Egypt, revealed the crucial role of the HNF1A genotype in HCC risk. Oncology Frontier invited Professor Mohamed Abdel Samie to discuss the potential value of this gene in HCC screening and the impact of metabolic factors. We look forward to future personalized treatment strategies targeting specific genotypes bringing new breakthroughs in the prevention and treatment of HCC.