The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a well-known carcinogen, however, the biological mechanism of carcinogenesis by TCDD has not been established. Recently, protein arginine methyltransferases (PRMTs) have been identified as secondary transcription co-activators and are proposed to be co-activators of aryl hydrocarbon receptors binding to xenobiotic response elements. Both PRMT1 and PRMT4 were also reported to be involved with carcinogenesis. The aim of this study was to identify cancer-related genes that are regulated by TCDD exposure and the effect of arginine methylation on TCDD toxicity by transfecting human hepatocarcinoma cells with PRMT1 and PRMT4 siRNA. By microarray analysis, 1,461 genes were up-regulated and 1,591 genes were down-regulated by TCDD exposure. Among the 16 up-regulated genes which had functions related to cancer or metastasis, 13 genes were confirmed by quantitative real time RT-PCR: ABCG2, NRP1, SOX5, BIRC3, CD109, CYP1A1, ERBB2, MTA1, FURIN, F3, PIK3R3, NPTN and NTN4. Co-inhibition of PRMT1 and PRMT4 resulted in decreased expression of eight of these genes, MTA1, ERBB2, SOX5, CD109, FURIN, NRP1, PIK3R3 and ABCG2, all of which have been reportedly involved in breast, ovary, prostate and lung cancers, and metastasis.The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent contaminants, causing various types of toxicity resulting in birth defects, teratogenesis, immunosuppression, tumor promotion and neuroendocrine disturbances 1 . Epidemiological studies in accidentally exposed populations have also established a link between high doses of TCDD and certain types of cancers and cardiovascular diseases 2 . Workers with the highest estimated levels of TCDD exposure showed a higher rate of all cancers 3 . The Seveso accident population showed a positive association between TCDD exposure and breast cancer 4 .TCDD is a proven carcinogen in rodent bioassays, and the induction of tumors by TCDD is tissue, sex, age, and species specific 5 . In mice, TCDD exposure during embryogenesis causes developmental abnormalities 6 , whereas exposure of adult rats results in an elevated incidence of hepatic carcinoma, and pulmonary and skin tumors 7 . TCDD is now regarded as a late-stage carcinogen for all types of cancer; however, the biological mechanism of TCDD-induced carcinogenesis has not been established 3 .It had been believed that the key mechanism of TCDD toxicity involved aryl hydrocarbon receptors (AhR). A few studies have reported changes in cancerrelated genes after exposure of cells to TCDD, for example, increased expression of focal adhesion genes or decreased expression of metastasis suppressor genes 8 .