In the past, the PHB gene function was mainly focused on anti-cell proliferation and antitumor effects. But the molecular mechanism of the PHB gene regarding saline and oxidative stresses is unclear. To study the role of AtPHB6 in salt and oxidative stress, AtPHB6 was cloned from A. thaliana. Bioinformatics analysis showed that AtPHB6 was closely related to AtPHB1 and AtPHB2, which are both type II PHB. RT-qPCR results indicated that the AtPHB6 in the leaves and roots of A. thaliana was obviously induced under different stress treatments. AtPHB6-overexpressing plants were larger and more lush than wild-type and mutant plants when placed under stress treatments during seed germination. The root length and fresh weight of AtPHB6 transgenic plants showed the best resistance compared to wild-type plants under different treatments, in contrast, the AtPHB6 mutants had the worst resistance during the seedling stage. AtSOT12 was an interacting protein of AtPHB6, which screened by yeast two-hybrid system. The interaction between the two proteins were further confirmed using in vitro pull-down experiments and in vivo BiFC experiments. Subcellular localization showed both AtPHB6 and AtSOT12 protein expressed in the nucleus and cytoplasm. The HO content in both the transgenic AtPHB6 and AtSOT12 plants were lower than that in the wild type under stresses. Thus, AtPHB6 increased plant resistance to salt stress and interacted with the AtSOT12 protein.