Salt stress represses the growth and development of plants that mainly depend on the continual propagation and differentiation of stem cells. WUSCHEL (WUS)/WUSCHEL-RELATED HOMEOBOX (WOX) family proteins determine stem cell fate in plants under ever-changing environments. It is not yet known how plant stem cell homeostasis is regulated under salt stress. Methionine synthase catalyzes the formation of methionine by methylating homocysteine in the one-carbon metabolism pathway. In this work, we investigated the role of Arabidopsis METHIONINE SYNTHASE 2 (AtMS2) in stem cell homeostasis under salt stress. The results showed that AtMS2 represses the stem cell maintenance of Arabidopsis in response to salt stress. Under normal growth conditions, AtMS2 is mainly localized in the cytoplasm. However, under salt stress, it exhibits significant accumulation in the nucleus. AtMS2 interacts with the WUS/WOX protein, and, together, they repress WUS/WOX expression by binding to its promoter. The mutation in AtMS2 resulted in enhanced salt tolerance. Therefore, AtMS2 might act as a key negative regulator to repress the stem cell maintenance and growth of Arabidopsis under salt stress.