ABSTRACT: Proton toxicity is one of the major environmental stresses limiting crop production, and becomes increasingly serious because of anthropogenic activities. To understand acid tolerance mechanisms, the plant growth, mineral nutrient accumulation and global transcriptome changes in soybean (Glycine max) in response to long-term acid stress were investigated. Results showed that acid stress significantly inhibited soybean root growth, but exhibited slight effects on the shoot growth. Moreover, concentrations of essential mineral nutrients were significantly affected by acid stress, mainly dependent on soybean organs and mineral nutrient types. The concentrations of phosphorus (P) and molybdenum (Mo) in both leaves and roots, nitrogen (N) and potassium (K) in roots and magnesium (Mg) in leaves were significantly decreased, respectively. Whereas, the concentrations of calcium (Ca), sulfate (S) and iron (Fe) were increased in both leaves and roots. Transcriptome analyses in soybean roots resulted in identifying 419 up-regulated and 555 down-regulated genes under acid conditions. A total of 38 differentially expressed genes (DEGs) were involved in mineral nutrient transportation. Among them, all the detected five GmPTs and GmZIPs, two GmAMTs and GmKUP genes, together with GmIRT1, GmNramp5, GmVIT2.1, GmSKOR, GmTPK5 and GmHKT1, were significantly suppressed. Moreover, the genes encoding transcription factors (e.g., GmSTOP2s and a GmPHL1), and genes involved in pH stat metabolic pathways were significantly up-regulated by low pH stress in soybean roots. Taken together, it strongly suggested that maintaining pH stat and mineral nutrient homeostasis are adaptive strategies of soybean responses to acid stress, which might be regulated by a complex signaling network.