Leukemia is a hematopoietic cancer and the treatment has many side effects. For this reason, herbal therapy is an alternative to reduce the side effects. Plucao or Houttuynia cordata Thunb., a local plant in Northern Thailand, has many biological activities including anti-cancer, antileukemic, anti-microbial, anti-oxidant, anti-inflammatory and immunomodulatory effects. The active components in Plucao are alkaloids and flavonoids. In this study, we extracted Plucao by distilled deionized water and alcohol and found that H.cordata ethanolic extract had total flavonoid content more than H.cordata water extract. Total flavonoid of H.cordata ethanolic extract was 224.90±2.80 mg QE/g dried H.cordata while total flavonoid of H.cordata water extract was 130.79±4.89 mg QE/g dried H.cordata. Moreover, H.cordata extracts could inhibit the proliferation of either Jurkat or U937 leukemic cell lines. The half maximal inhibitory concentration (IC50) values of H.cordata extracts were between 403.3 to 445.1 mg/ml and 386.2 to 416.4 mg/ml, respectively. In addition, our cytokine study found that H.cordata extract especially H.cordata ethanolic extract substantially reduced the Tumor Necrosis Factor-alpha (TNF-α). Therefore, these finding highlight the fact that H.cordata has anti-leukemic activity and suggest its use as an alternative medicinal plant in the treatment of leukemia.