Eight methylated nordihydroguaiaretic acids containing a 4- or 2-nitroimidazole moiety were synthesized as leads against hepatocellular carcinoma. Four of these conjugated compounds possessing a polyethylene glycol tether for improvement of their aqueous solubility. These nordihydroguaiaretic acid–nitroimidazole conjugates were found to inhibit hepatocellular carcinoma Hep3B cells under 20% oxygen and hypoxia conditions with IC50 values between 10–20 μM