Hepatoma is caused by many factors including alcohol, chemicals, viral infection, and chronic inflammation. Cytochrome P450 polymorphism plays an important role in its pathogenesis. CYP2D6, CYP2E1, and CYP1A1 have been identified to be related with hepatic carcinogenesis and tumor size and stage. However, no studies have been performed on CYP2C9, a major CYP in the liver and hepatoma.To identify if there is polymorphism of CYP2C9 in a HepG2 cell line.A pair of primers was used to clone CYP2C9 exon 3 region and subsequently sequenced. The sequence was compared to normal CYP2C9 for identification of any mutation.A point mutation was identified. It was located in the amino acid number 144 of CYP2C9 protein with the change of normal amino acid arginine into cysteine, which is the same as identified in poor metabolism patients as homozygous CYP2C9*2.There is a mutation (CYP2C9*2/ CYP2C9*2) in a HepG2 cell line. Thus, polymorphism of CYP2C9 may also be involved in the carcinogenesis of hepatoma as CYPs2D6 and 2E1.