Thiophenes, a class of polycyclic aromatic compound (PAC), which contain a sulfur in one of the rings, are components of petroleum. The Erika oil spill (December 1999) impacted 400 km of Atlantic French coast. The Erika fuel is an heavy fuel containing 3–4% sulfur and sulfur compounds such as thiophenes. It has been reported that water and sediments were contaminated by dibenzothiophene (DBT). Analysis of DNA adducts in fish liver and mussel digestive gland, living in sites impacted by Erika oil spill, has revealed DNA adduct pattern different from a classical PAH contamination. Few studies report biological activities of thiophenes in the environment (1). In this study, we have analyzed the cytotoxicity and the genotoxicity of six thiophenes [benzo(b)]thiophene (BT), dibenzothiophene (DBT), benzo(b)naphtha(2,1-d)thiophene (BNT), 6-methylbenzo(b)naphtha(2,1-d)thiophene (6-CH3BNT), dinaptho(2,1-b;1′,2′-d)thiophene (DNT), and diphenanthro(9,10-b;9′,10′-d)thiophene (DPT) in liver human cell line (HepG2). Whatever the doses, BT, DPT, and DNT do not form DNA adducts in HepG2 cell line. On the contrary, DBT, BNT, and 6-CH3 BNT induced DNA adduct formation. Two individual adducts are formed with DBT and one with BNT. The 6-CH3BNT which is the alkylated homologue of BNT also forms two adducts which are persistent after 48 h of treatment. Our results show that some thiophenes are genotoxic for HepG2 cells.