Although the relative extent of xanthine oxidoreductase (XOR) varies considerably in human tissues, the greatest specific activity is reported in the liver and intestines. Unlike murine models, where primary hepatocytes are readily available, human counterparts are not. As such, investigators often utilize the human carcinoma cell line HepG2 for in vitro experimentation as these cells proliferate well in culture medium. Some of the studies using HepG2 cells for proof-of-principal experimentation focus on uric acid (UA) and/or XOR activity. However, it has been reported that hepatocellular carcinoma diminishes XOR expression to nearly unmeasurable levels when compared to normal cell counterparts which posits the question of validity in the context of using HepG2 cells for XOR/UA assessments. As such, we closely examined XOR expression, protein abundance, and enzymatic activity in HepG2 cells and compared these results to an immortalized murine hepatocyte line (AML12) as well as murine liver homogenate. We report the absence of detectable XOR message, protein, and enzymatic activity in HepG2 cells. Since cellular XOR expression has been reported to be stimulated by hypoxia and serum starvation, we then exposed both AML12 and HepG2 cells to hypoxia (1% O