The denitrification desulfurization system can be used to remediate wastewater containing carbon, nitrogen, and sulfur. However, the relationship between autotrophic and heterotrophic bacteria remains poorly understood. To better understand the roles and relations of core bacteria, an expanded granular sludge bed (EGSB) reactor was continuously operated under autotrophic (stage I), heterotrophic (stage II) and mixotrophic (stages III–VII) conditions with a 490-day period. Stage IV represented the excellent S0 recovery rate (69.5%). The different trophic conditions caused the obvious succession of dominant bacterial genera. Autotrophic environment (stage I) enriched mostly Thiobacillus, and heterotrophic environment (stage II) was dominated with Azoarcus and Pseudomonas. Thauera, Arcobacter and Azoarcus became the predominant genera under mixotrophic conditions (stage III-VII). Strains belonged to these core genera were further isolated, and all seven isolates were confirmed with denitrifying sulfur oxidation capacity. Heterotrophic strain HDD1 (genus of Thauera) possessed both the highest sulfide degradation and S0 recovery rates. Expression levels of cbbM and gltA genes were positively related with the autotrophic and heterotrophic conditions, respectively. NirK gene was highly expressed between log 3.7–log 4.3 during the entire run. Expression of both sqr and soxB genes were closely related with sulfur conversion. More than 57.5% of S0 recovery rate could be obtained as sqr gene expression was greater than log 3.2, and while, sulfate was the primary form as soxB gene expression higher than log 3.9. The correlation between core microbial genera was very low from network, indicating a complex and non-specific mutualistic network between bacterial functional groups under each nutrient condition, and a stable coexistence state was possibly formed through utilizing each the secondary or waste metabolites in the mixotrophic conditions. This relationship was beneficial to the stability of the microbial community structure in the denitrification desulfurization system.