Toxaphene is a bioaccumulative, persistent, and toxic pollutant. Toxaphene is one of the 12 priority of Persistent Organic Pollutants (POPs) intended for global action by the United Nations Environment Program (UNEP) Governing Council. POPs are manmade synthetic chemicals highly resistant to biodegradation, with a high affinity for bioaccumulation (due to their hydrophobic and/or lipophilic nature) and biomagnification in the environment and living organisms, including humans. Once deposited in humans (mainly in adipose tissue), they form stable compounds that result in a lasting toxic body burden. Most human populations are exposed to mixtures of POPs originated either from local or remote sources. Toxaphene is ubiquitous in air, water, soil, and biological matrices, as well as in major environmental compartments. Toxaphene has effects on various organs such as thyroid, bone, skin, kidneys, and blood cells and especially, revealed strong toxicity to liver. In this study, we identified genes related to hepatotoxiciy induced by toxaphene in human hepatocellular carcinoma (HepG2) cells using microarray and gene ontology (GO) analysis. Through microarray analysis, we identified 1,647 up- and 2,251 down-regulated genes changed by more than 1.5-fold and P-values 0.001 by toxaphene. And after GO analysis, we determined several key pathways which known as related to hepatotoxicity such as MAPK signaling pathway, complement and coagulation cascades, tight junction. Thus, our present study suggests that genes expressed by toxaphene may provide a clue for hepatotoxic mechanism of toxaphene.