The discovery of Helicobacter hepaticus as a causal agent of hepatitis and hepatocellular carcinoma (HCC) in mice has stimulated interest in looking for Helicobacter species in human liver samples. In this study, we searched for association between H. pylori and HCV-related liver disease. Liver specimens were collected from eighty-five patients; they were divided into five different groups according to liver pathology (METAVIR system). Group I (the 1st control group) consisted of 16 patients with chronic hepatitis C without histological activity. Group II consisted of 25 patients with chronic active hepatitis C, Group III, 17 patients with HCV-related cirrhosis and Group IV, 16 patients with HCV-related cirrhosis and HCC. Group V (2nd control group) consisted of 11 patients suffering from gastro duodenal and gall bladder diseases but negative for HCV. All cases were tested by polymerase chain reaction on liver samples for the presence of H. pylori DNA Cag A gene. Routine biochemical, radiological and RT-PCR for HCV RNA were also performed for all cases. The positivity of H. pylori PCR CagA gene in liver tissue was directly proportional to the severity of liver pathology, this being 75%, 52.9% and 32% in groups IV, III and II, respectively, which was more significant than the 1st and 2nd control groups (P < 0.001). There was a significant difference between H. pylori PCR values when compared to METAVIR staging (F) in different groups (P = 0.001). Helicobacter pylori PCR (Cag A gene) was positive in about 28.2% cases of late fibrosis (F3 + F4) while positivity was (5.9%) in early fibrosis (F1 + F2) (P = 0.0001). There was significant difference between H. pylori PCR (Cag A gene) in liver tissue and METAVIR activity in different groups (P = 0.002) as most of H. pylori PCR-positive cases were METAVIR activity A1 and A2 (15.3% and 12.9%, respectively). There was no association between H. pylori PCR and quantitative HCV RNA (P = 0.531). Also there was no significant difference of Child-Pugh staging in the H. pylori PCR-positive group when compared to the negative group (P = 0.996). There may be an association between the presence of H. pylori (Cag A gene) in the liver and disease progression in HCV-related chronic hepatitis and cirrhosis with and without HCC.