Growing evidence supports the notion that serum NAPDH oxidase 2 (NOX2) is an important regulator that contributes to the initiation and progression of various types of diseases. However, so far, it remains elusive about the relationship between levels of serum NOX2 and HBV-related diseases. The overall purpose of the study is to get a better insight into whether or not serum NOX2 is involved in HBV-related disorders. Serum levels of NOX2, from 105 patients with chronic hepatitis B, 58 patients with HBV-related cirrhosis, 48 patients with HBV-related hepatocellular carcinoma and 104 healthy individuals, were measured with sandwich ELISA kits that we developed. In this study, we found that NOX2 values were significantly higher in patients compared to healthy control (P < 0.01) and that the levels of serum NOX2 were significantly correlated with the serum levels of superoxide dismutase (SOD), interleukin-6 (IL-6), interferon-stimulated gene 15 (ISG15), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) in chronic hepatitis B, cirrhosis and hepatocellular carcinoma patients. Interestingly, we found that a significant positive correlation between NOX2 and HBV viral load only in patients with chronic hepatitis B and cirrhosis. Therefore, Serum NOX2 levels maybe an important indicator of the pathogenesis of progression of HBV-related disorders.