Hyperthermia is widely used to treat patients with various cancers. Here, the effects of heat stress at 41C for 30 min (mild hyperthermia) on the gene expression in OUMS-36 human normal fibroblast cells were investigated using an Affymetrix GeneChip system. The cells were treated with mild hyperthermia, followed by incubation for 0, 1, or 3 h at 37C. No cell death was observed in the mild hyperthermia-treated cells. On the other hand, many genes that were differentially expressed by a factor 1.5 or greater were identified in the cells treated with the mild hyperthermia.