We used voxel-based independent sample t-test to investigate differences of DKI and resting-state fMRI parametric maps between KIBRA rs17070145 polymorphism in 163 young adults. Mediation analysis was used to explore the association between the KIBRA polymorphism, brain and working memory. We observed that KIBRA C-allele carriers had increased AD, RD, MD and decreased FA, MK, RK, ALFF compared with KIBRA TT homozygotes. The MK, RK of the left precuneus mediated the association between the KIBRA polymorphism and the working memory performance. These findings may be useful in understanding the neural mechanisms of KIBRA and provide a biological pathway of gene-brain-behavior.