We conducted a case-control study performed in the China-Japan Union Hospital of Jilin University, China from 2010 to 2015 to investigate the seroprevalence of Helicobacter pylori infection in patients with chronic hepatitis B. The cases were 853 patients with chronic hepatitis B who were sex and age matched to 729 healthy controls. All subjects were tested for the presence of serum anti-H. pylori-IgG. H. pylori infection was more prevalent in patients with chronic hepatitis B (59.6%), chronic Hepatitis B virus (HBV)-related cirrhosis (77.3%), and Hepatocellular Carcinoma (HCC) (80.3%) than in healthy controls (43.3%) (χ2=35.708, χ2=53.175, χ2=29.501, respectively; P<0.05). The differences in H. pylori prevalence among the case groups by the serum viral load of HBV DNA were not statistically significant (P>0.05). No significant difference among groups by genotype was detected (P>0.05). H. pylori infection was more highly prevalent in cirrhosis patients with complications such as hepatic encephalopathy (69.6%), peptic ulcers (61.0%), and upper gastrointestinal hemorrhage (78.7%) than in patients without complications (χ2=7.713, χ2=4.293, χ2=16.517, respectively; P<0.05). Whether H. pylori act synergistically with HBV for the progression from chronic hepatitis B to cirrhosis and HCC requires further research.