Troglitazone is an anti-diabetic agent that improves hyperglycemia by reducing peripheral insulin resistance in type II diabetic patients. Troglitazone has been shown to cause growth inhibition of various normal and cancerous cells. However, the molecular mechanism by which troglitazone affects the growth of these cancer cells remains unclear. Here, we report that troglitazone treatment of Hep 3B human hepatocellular carcinoma cells resulted in dose-dependent growth inhibition. Analysis of cell cycle distribution by flow cytometry showed that the number of apoptotic cells was increased in a dose-dependent manner in response to troglitazone treatment. cDNA microarray analysis showed a number of differentially expressed genes in response to troglitazone. Among the upregulated genes, hypoxia-inducible factor 1 (HIF-1)-responsive RTP801 was induced in a dose-dependent manner. We also observed HIF-1 accumulation by immnocytochemistry after troglitazone treatment. These results strongly suggest that RTP801 might be involved in troglitazone-induced apoptosis in Hep 3B cells.