Halophilic marine anammox bacteria (MAB)-based sulfide-based autotrophic denitratation and anammox (MSADA) process was investigated to treat seawater-based wastewater under different influent sulfide to nitrate (S/N) ratios. This study firstly presented a novel method with merely inoculating halophilic MAB-based sludge to start up the MSADA process in a sequencing batch reactor. Nitrogen and sulfide could be efficiently removed from seawater-based wastewater at the total nitrogen removal efficiency of 93.7% and sulfide removal efficiency of 100% under the optimum S/N ratio of 0.75 in the MSADA process. Meanwhile, anammox and sulfide-based autotrophic denitrification respectively accounted for about 94.2% and 5.8% of the total nitrogen removal with the high nitrite accumulation efficiency of 92.7%. At the optimum S/N ratio of 0.75, “Candidatus Scalindua” (3.28%), Sulfurimonas (18.68%) and Sulfurovum (11.04%) were the main functional microorganisms, which had the excellent salt tolerance. The dominating functional microorganisms dynamically changed with the different S/N ratios. The microbial community composition was similar and steady when the S/N ratios were 0.33–0.75. Nitrate reductase activity was much higher than nitrite reductase activity in the MSADA system, which made it possible to keep the NO3−-N reduction products at NO2−-N level and provide sufficient NO2−-N for MAB. The coupled process provides a new perspective in the treatment of seawater-based wastewater.