Heat shock factor 1 (HSF1) is the key protein in regulating stress response. It can be activated under heat，oxidative or another stress conditions. Dominant-positive and dominant-negative HSF1 are two types of HSF1 mutants. Both of them gain the DNA binding activity in the absence of stress. In addition，dominant-positive HSF1 acquires transcriptional activity，which dominant-negative HSF1 does not acquire. In this paper，the progress of using these HSF1 mutants in the research of cancer，neurodegenerative disorders and cardiovascular diseases will be discussed.