Abstract: Background: Liver cancer is a widespread malady in Northern parts of Egypt, in which industrial and municipal heavy metals pollutants contaminate both water and soil used for growing edible field and vegetable crops. Materials and Methods: Case-control studies were carried out in three locations in North Delta region (Dakahlia, Kafr El-Sheikh and Damietta governorates) where lead, cadmium, arsenic and mercury are common pollutants. Clinical examination of 143 HCC patients living in heavy metals-polluted areas and 171 healthy individuals living in relatively clean, non-polluted areas were carried out. The investigation was confirmed by fine needle aspiration cytology, histological examination and alpha-fetoprotein level analysis. Heavy metals assay in blood, plants, soil and water were carried out using the atomic absorption spectrophotometry technique and data were statistically analyzed. Results: Demographic and clinical data of patients with HCC show that levels of heavy metals under investigation (Pb, Cd, As and Hg) were significantly higher in the blood of HCC patients compared to control subjects. Conclusion: Results address a strong correlation between the occurrence of these heavy metals in blood of HCC patients and their levels in irrigation water, soil and edible plants.