Herbicides, known as weed killers, used to kill unwanted plants, leaving the desired crop relatively unharmed. They are widely used in agriculture and account for about 70% of all agricultural pesticide use. Among environmental factors hypothesized to increase the risk of hepatocellular carcinoma (HCC) are exposures to pesticides. Because a major segment of the population in Egypt is employed in agriculture, raising the possibility that exposure to pesticides is an additional risk factor for (HCC), which is the most common malignant tumors worldwide. So, the present work studied the possible association between some herbicides exposure used at least within the past 12 months as (2,4,5-trichlorophenoxyacetic acid) and (N- glycerine isopropyl ammonium) and occurrence of (HCC) in some delta areas in Egypt. The study was conducted from the 1st of January 2014 to 1st of July 2015. It involved 100 cases were recruited from Hepatology, Gastroenterology and infectious disease of Al-Azhar University Hospital (New Damietta).  In addition to 50 subjects served as a control group. After free informed consent to participate in this study and within one hour after arrival to Hepatology, Gastroenterology and Infectious Disease Hospital, 10 mL of blood were collected and the serum was divided into three aliquots. One for extraction of (2,4,5-trichlorophenoxyacetic acid and N- glycerine isopropyl ammonium) residues by using high performance liquid chromatography (HPLC) and two of which were stored at -8C °  for the following assays to all subjects, (HCV and HBV) and serum alpha-fetoprotein. Cases and controls were subjected to a standardized questionnaire. Clinical examination to all groups with a special attention to; manifestation of liver disease, then diagnosis of (HCC) by; abdominal ultrasonography, computerized tomography and magnetic resonance imaging beside histopathology for confirmation of some case were done. In general (HCC) in the present study, has a strong possible correlation with exposure to some herbicide (2,4,5-trichlorophenoxyacetic acid) (70.0%) and (N- glycerine isopropyl ammonium) (80.0%) which is statistically significant and hepatitis c virus is positive in (80.0%) and to some degree hepatitis B virus is positive in (40.0%) which acts as additive effects for HCC especially among rural area, which constitutes  (95.0%) of  the present sample.