It has been suggested that Phyllanthus amarus may be helpful in the treatment of hepatitis B virus infection. We studied the effect of an aqueous extract of P. amarus on the cultured hepatoma cell line HepA2. This cell line had been transfected with tandemly arranged HBV DNA and continued to synthesize and secrete both HBsAg and HBeAg. Extract of P. amarus reversibly inhibited cellular proliferation and suppressed HBsAg production but not HBeAg production in HepA2 cells. We also found that P. amarus suppressed HBsAg gene expression at mRNA level in a time-dependent manner, and selectively abolished the HBsAg gene promoter driven CAT activity. Our results demonstrate that P. amarus contains some active components which can suppress the HBsAg gene expression in human hepatoma cells. Such suppression may contribute the antiviral activity of P. amarus in vivo.