The relationship between serum viremia and the development of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-related cirrhosis remains unclear. We aimed at calculating odds ratios (OR) for the presence of HCC over a range of HBV DNA levels in these patients. Patients were identified retrospectively and 155 pairs of matched, treatment-naive HBV-related cirrhotic patients with and without HCC were recruited. Their serum HBV DNA levels were measured at HCC diagnosis, or at the equivalent age in non-HCC patients, and correlations between the presence of HCC and different DNA levels were calculated using conditional logistic regression. The median HBV DNA level was significantly higher in HCC patients than in non-HCC patients (5.15 vs 4.83 log(10) copies/mL, P = 0.024). The overall OR for HCC in patients with HBV DNA >= 3 log(10) copies/mL was 2.13, compared with patients with levels < 3 log(10) copies/mL. Compared with patients with < 3 log(10) copies/mL, the OR for HCC were 2.39 and 2.61 for patients with 4 to < 5 and 5 to < 6 log(10) copies/mL, respectively, while the OR for DNA levels of >= 6 log(10) copies/mL were not significantly different. In HBV-related cirrhosis, a detectable serum HBV DNA was associated with the presence of HCC, but the likelihood of having HCC did not successively increase with increasing serum HBV DNA levels: patients with serum HBV DNA levels between 4 and < 6 log(10) copies/mL were most likely to present with HCC.