Human major histocompatibility complex (MHC) class I expression is usually suppressed in neuronal cells and neuroblastoma cells. In the present study, we analyzed the effect of a flavonoid antioxidant, silymarin, on the induction of MHC class I molecules in human neuroblastoma line cells. Treatment of neuroblastoma cells with silymarin resulted in the expression of MHC class I molecules. Silymarin treatment enhanced the transcriptional activity of the reporter construct containing MHC class I promoter truncated within -428 bp of transcription initiation, but not the construct containing the promoter truncated within -284 bp. Because an E-box element is located between -428 and -285 bp of the transcription initiation, results suggest that silymarin acts on the enhancer activity of the E-box in the MHC class I promoter. Our findings indicate that silymarin induces the transcriptional factors to enhance the MHC class I promoter through the class I E-box element.