Heat shock transcription factors (Hsfs) are the central regulators of the heat shock (HS) stress response in all eukaryotic organisms. HsfA2 is one of the Arabidopsis class A Hsfs, and the induction of HsfA2 expression in response to HS stress is highest among all 21 Arabidopsis Hsfs. In this study, it is reported that basal and acquired thermotolerance was significantly enhanced in high-level HsfA2-overexpressed transgenic lines (El2Omega::HsfA2) in comparison with wild-type plants. By contrast, the dominant negative mutants of HsfA2 (El2Omega::HsfA2DeltaC264) plants displayed reduced thermotolerance. These results indicate that the HsfA2 gene plays a role in the HS stress response. Microarray analysis of the El2Omega::HsfA2 plants identified putative target genes, which included HS stress-inducible genes and other stress-responsive genes. Salt and osmotic stress induced HsfA2 gene expression. In fact, the El2Omega::HsfA2 plants showed enhanced tolerance to these stresses, suggesting that HsfA2 was involved in multiple stress tolerance. El2Omega::HsfA2 plants showed accelerated callus growth from root explants compared with the wild type, unlike the El2Omega::HsfA2DeltaC264 plants whose growth was delayed. These observations suggest that HsfA2 plays, in addition to its role in stress tolerance, an important role in cell proliferation.