In this work, the interaction mechanisms between an autotrophic denitrification (AD) and heterotrophic denitrification (HD) process in a heterotrophic-autotrophic denitrification (HAD) system were investigated, and the performance of the HAD system under different S/Ac− molar ratios was also evaluated. The results demonstrated that the heterotrophic-combined-with-autotrophic denitrification process is a promising technology which can remove chemical oxygen demand (COD), sulfide and nitrate simultaneously. The reduction rate of NO3− to NO2− by the HD process was much faster than that of reducing NO2− to N2, while the reduction rate of NO3− to NO2− by the AD process was slower than that of NO2− to N2. Therefore, the AD process could use the surplus NO2− produced by the HD process. This could alleviate the NO2−–N accumulation and increase the denitrification rate. In addition, the inhibition effects of acetate on AD bacteria and sulfide on HD were observed, and the inhibition was compensated by the promotion effects on NO2−. Therefore, the processes of AD and HD seem to react in parallel, without disturbing each other, in our HAD system.