In this study, aerobic co-composting of tylosin fermentation dregs (TFDs) and sewage sludge with different adding concentrations of copper (Cu) was investigated to inspect the fate of antibiotic resistance genes (ARGs), metal resistance genes (MRGs) and mobile genetic elements (MGEs). Results showed that two concentrations of Cu did affect not only the abiotic factors but the relative abundances of resistance genes. High concentration of Cu inhibited the metabolic capacity of microbial community and the nitrogen-fixing process while had little effect on the degradation of TYL and TOC. The abundance of ermT, mefA, mphA increased partly attributed to the toxic effects and co-selective pressure from heavy metal reflected by MRGs. There was significant correlation among some environmental factors like pH, bio-Cu, organic matters and ARGs.