Ca 2+/CaM signal transduction pathway is well known to help plants to adapt to the environmental stress. However, our knowledge on the function proteins of Ca 2+/CaM pathway in peanut remains limited. Here, using yeast two hybrid methods, we identified a novel calmodulin4 (CaM4) binding protein S-adenosyl-methionine synthetase1 (SAMS1) in peanut. The expressions of AhSAMS1 were obviously induced by Ca 2+, ABA and salt stress. To elucidate the function of AhSAMS1, physiological and phenotypic analyses were applied between wild type and transgenic materials. Overexpression of AhSAMS1 significantly increased Spd and Spm synthesis while decreased the contents of ethylene, thus eliminating excessive ROS in the transgenic lines under salt stress. Consistent with the induced expressions of SOS and NHX genes, AhSAMS1 reduced the uptake of Na + and the leakage of K + from mesophyll cells, and was less sensitive to salt stress during early seedling growth. Transcriptomics combined with epigenetic regulation uncovered the relationships between DEGs and DMRs, which raised the salt tolerance and plants growth. Together, our findings support a model in which the role of AhSAMS1 on ROS-dependent regulation of ion homeostasis was enhanced by Ca 2+/CaM while AhSAMS1-induced methylation was regulated by CaM, thus providing a novel strategy to enhance plant salt tolerance.