Sulfur-driven　autotrophic　denitrification　coupled　with　anammox　(SPDA)　is　a　promising　process　for　autotrophic　nitrogen　removal,　but　autotrophic　microorganisms　are　challenging　to　retain　in　wastewater　treatment　units.　In　this　study,　a　single-stage　mixotrophic　denitrification　coupled　with　anammox　(MDA)　process　was　established　in　an　up-flow　anaerobic　sludge　bed　reactor　with　Thiothrix-hydroxyapatite　coupled　particles.　The　advancement　of　the　sludge　granulation　process　effectively　strengthened　the　resistance　of　the　MDA　system　to　environmental　stresses,　and　the　SPDA-dominated　nitrogen　removal　process　achieved　a　total　nitrogen　removal　efficiency　of　88.6　%,　a　nitrogen　removal　rate　of　0.432　KgN/m3/d　at　temperatures　as　low　as　12.8　degrees　C　and　an　organic　loading　rate　of　0.63　KgCOD/m3/d.　Interestingly,　the　ecological　niche　integration　of　sulfur　oxidizing　bacteria　(SOB),　anammox　bacteria　and　heterotrophic　denitrifying　bacteria　in　the　granular　sludge　was　observed　during　long-term　operation.　The　FISH-CLSM　results　revealed　the　spatial　distribution　of　functional　microorganisms　in　the　granular　sludge　and　the　potential　pollutant　transformation　mechanism.　The　aggressive　growth　of　SOB　dominated　by　Thiothrix　constructed　a　biological　wall　at　the　periphery　of　the　granules,　which　ensured　their　priority　for　nitrate　acquisition,　supplied　nitrite　to　the　internal　anammox　bacteria,　and　acted　as　an　important　barrier　against　the　shock　of　organic　loads.　Overall,　this　study　presents　a　novel　granulation　approach　for　the　biological　treatment　of　sulfur-containing　wastewater,　highlighting　the　efficacy　of　functional　integration　within　Thiothrix-hydroxyapatite　coupled　particles　as　an　effective　strategy　to　resist　environmental　stress.