The effect of variable sodium concentrations on the anaerobic digestion performance of Sargassum sp. was investigated, and the variation in bacterial and archaeal communities was analyzed by high-throughput gene sequencing. Results showed that the maximum methane yield of 290.41 +/- 34.21 mL of CH4 g(-1) of volatile solids was obtained at a sodium concentration of 4.42 g L-1, increased by 38.1% compared to the control group. Meanwhile, higher volatile fatty acids production was observed at the sodium concentration of 4.42 g L-1. The inhibitory concentration values of 10%, 50%, and 90% occurred at the sodium concentrations of 6.3, 11.3, and 18.7 g L-1, respectively. The hydrolytic, acidogenic, and acetogenic bacteria and the hydrogenotrophic methanogens could normally metabolize at sodium concentrations of 2.4624.08 g L-1, whereas the acetoclastic methanogens were severely inhibited at sodium concentrations greater than 20.15 g L-1. The microbial community structure showed that Paludibacter and Fibrobacter played a key role in the step of acidogenesis/acetogenesis at sodium concentration of 4.42 g L-1, while Defluviitalea and Levilinea were the major acidogenic/acetogenic bacteria at sodium concentration of 20.15 g L-1. Methanosaeta and Methanosarcina were the predominate methanogens at sodium concentration of 4.42 g L-1.