In this study, using LAD ligation in HSF1 KO and TG mice, together with hypoxic treatment in NRCMs infected with adenovirus of HSF1 SiRNA, we uncovered that deficiency of HSF1 deteriorated cardiac hypertrophy and cardiac dysfunction after MI through enhancing the activity of JAK2/STAT3 signalling. Here, JAK2 is linked to cardiac hypertrophy.