An upflow anaerobic sludge blanket reactor was employed to treat saline sulfate wastewater. Mesophilic operation (35 ± 0.5 °C) was performed with hydraulic retention time fixed at 16 h. When the salinity was 28 g L−1, the chemical oxygen demand and sulfate removal efficiencies were 52 and 67 %, respectively. The salinity effect on sulfate removal was less than that on organics removal. The methane productions were 887 and 329 cm3 L−1 corresponding to the NaCl concentrations of 12 and 28 g L−1, respectively. High salinity could stimulate microbes to produce more extracellular polymeric substances (EPSs) and granulation could be performed better. Besides, with the high saline surroundings, a great deal of Na+ compressed the colloidal electrical double-layer, neutralized the negative charge of the sludge particles and decreased their electrostatic repulsion. The repulsion barrier disappeared and coagulation took place. The maximum size of granules was 5 mm, which resulted from the coupled triggering forces of high EPSs and Na+ contents. Sulfate-reducing bacteria (SRB) were dominant in the high saline surroundings while the methane-producing archaea dominated in the low saline surroundings. The SRB were affected least by the salinity.