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Objective This study explored the association between the risk of carbamazepine ( CBZ)-induced Stevens- Johnson syndrome ( SJS)/toxic epidermal necrolysis ( TEN) and CBZ dose, dose-adjusted concentration, and ABCB1 , CYP3A4 , EPHX1 , FAS , SCN1A , MICA, and BAG6 polymorphisms in patients of Han ethnicity with epilepsy who were living in northeastern China. Materials and methods We determined the genotypes of patients with CBZ- SJS/ TEN and CBZ-tolerant patients, who were used as controls, for ABCB1 , CYP3A4 , EPHX1 , FAS , SCN1A , MICA, and BAG6 polymorphisms by polymerase chain reaction ( PCR) amplification and direct sequencing. We measured the steady-state serum CBZ concentrations using fluorescence polarization immunoassay for the control patients. Results We observed statistically significant differences in EPHX1 c.337T>C polymorphisms between patients with CBZ- SJS/ TEN and CBZ-tolerant controls in terms of allelic and genotypic frequencies (p = 0.011 and p = 0.007, respectively). The C allele and the C- G diplotype of EPHX1 may play important roles in increasing the risk of CBZ- SJS/ TEN development (odds ratio [ OR] 0.478, 95% confidence interval [ CI] = 0.267-0.855, p = 0.011; OR = 0.213, 95% CI = 0.049-0.930, p = 0.025, respectively). We did not observe any significant associations between ABCB1 , CYP3A4 , EPHX1 , FAS , SCN1A , MICA or BAG6 genes and CBZ dose or dose-adjusted concentration in CBZ-tolerant patients. Significance We found a significant association between EPHX1 c.337T>C polymorphisms and the development of CBZ- SJS/ TEN in patients of Han ethnicity living in northeastern China. EPHX1 c.337T>C polymorphisms may contribute to the risk of severe CBZ- SJS/ TEN by increasing the concentration of a CBZ metabolite, CBZ-10,11-epoxide, in patients with epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section . [ABSTRACT FROM AUTHOR]