Heat shock factor 2 (HSF2) is one of the most important regulators affecting stress mechanisms, and is frequently amplified in the ubiquitin proteasome pathway. Despite its significance, the mechanisms which regulate HSF2 expression remain unclear. In the present study, we describe the existence of a negative autoregulatory mechanism of HSF2. Transfection assays demonstrated that HSF2 decreased endogenous HSF2 mRNA expression in human K562 erythroleukemia cells. Luciferase reporter assays revealed that HSF2 inhibited the activity of its own promoter in a dose-dependent manner and that the downstream region (-1.5 kb) relative to the transcription start site was responsible for this inhibitory effect. Furthermore, chromatin immunoprecipitation (ChIP) assat indicated that HSF2 is directly recruited onto its own promoter, which contains a putative heat shock element (HSE). Collectively, the findings of our studys suggest that HSF2 contributes to its own expression by forming a negative autoregulatory loop.