To confer the influence of Hsp22 on pathogenesis of SCA3/MJD. GMR-GAL4 and elav-GAL4 system SCA3/MJD transgenic Drosophila models were constructed by using the promoter GMR-GAL4 and elav-GAL4 which drive target selective gene expression in developing eyes and neurons, respectively. Then, Hsp22 protein was overexpressed in SCA3/MJD transgenic Drosophila models at different levels by genetic methods and heat shock reaction. Overexpression of endogen Drosophila Hsp22 can notably suppress the neurotoxicity of MJDtr-Q78 protein, and the level of Hsp22 expression was in consistent with rehabilitation for neurodegeneration of Drosophila eyes, and extension of Drosophila lifespan. It is firstly confirmed that expression of Hsp22 protects the SCA3/MJD from neurodegeneration on Drosophila models, which might contribute to a potential therapeutic effect on SCA3/MJD.