The persistent inflammation aggravated by a disordered immune response is considered to be the major cause of CD4 T cell depletion in lymphoid tissue， which impels the progression of AIDS. Here， we report that heat shock factor 1 (HSF1) works as an innate repressor of HIV-induced inflammation. The activation of HSF1 was found to accompany inflammation during HIV infection. Further research uncovered that HSF1 activation inhibited HIV-induced inflammation. In addition， HSF1 overexpression suppressed the inflammatory response induced by HIV， while HSF1 deficiency exacerbated that inflammation. Mechanistically， HSF1 was found to compete with nuclear factor-κB (NF-κB) in the nucleus. Generally， our report highlights that HSF1 is an important host factor in regulating HIV-induced inflammation and may work as a potential target for curing AIDS.