Objective: Heat shock factor-1 (Hsf-1) controls the expression levels of heat shock proteins (hsps), that play a defensive role on the neurodegeneration by solubilizing and refolding pathogenic proteins. To reveal the function of Hsf-1 on the skeletal muscle pathology of spinal and bulbar muscular atrophy (SBMA), an adult-onset motor neuron disease, here we investigate the changes in hsp regulation in the skeletal muscle of heterozygous Hsf-1 knockout SBMA mice. Methods: We performed western blotting and Immunohistochemistry of skeletal muscle from wild-type; AR-97Q (SBMA model: 97Q Tg/-, Hsf-1 +/+); and AR-97Q Hsf-1 +/- (heterozygous Hsf-1 knockout SBMA: 97Q Tg/-, Hsf-1 +/-) mice using anti-Hsf-1, anti-Hsp72, anti-Nfya, anti-Sp1, anti-p53, anti-Tbp and anti-polyglutamine antibodies. Results: While Hsp72, the inducible form of Hsp70, was downregulated in the spinal cord on western blot analysis, the expression level of this chaperone in skeletal muscle was unaffected despite Hsf-1 depletion. Additionally, the reduction of Hsf-1 did not enhance the pathogenic AR accumulations in the skeletal muscle of SBMA model mice. Surprisingly, Nfya and Sp1 were upregulated in the skeletal muscle of AR-97Q mice compared with wild-type mice both in immunohistochemistry and western blot analysis. Furthermore, this phenomenon was enhanced by the heterozygous Hsf-1 depletion. In contrast to the skeletal muscle, neither Nfya nor Sp1 was upregulated by Hsf-1 depletion in the spinal cord of AR-97Q or in heterozygous Hsf-1 knockout AR-97Q mice. Conclusions: These results suggest that skeletal muscle of SBMA mice may have a compensative mechanism on the pathogenic AR-mediated dysregulation of hsps.