Previous work from this laboratory has cloned a novel gene NOR1 and showed its extensive expression in normal tissues and down-regulation in carcinomas. To further investigate its downstream target genes and better understand its function, NOR1 was over-expressed in HepG2 hepatoma cells and global changes in gene expressions from a stable line were identified by cDNA microarrays. The results discovered 59 genes up-regulated in these cells compared with the original cells, including Grb2, HBP17, TNFRSF11B genes that have been implicated in tumorigenesis and cancer development. In addition, 103 down-regulated genes were also identified, including genes encoding Bik, MAP2K6 and ZFP95 proteins. The expression patterns of certain genes identified by microarrays were validated by quantitative real-time PCR and the results showed that expression difference were statistically significant (P < 0.05). These data suggest that NOR1 may influence the biology and cancerous behaviors of HepG2 cells by regulating expression of a set of genes involved in signal transduction, cell cycle regulation, transcription and translation controls.