Understanding the main drivers that affect the spread of antibiotic resistance genes (ARGs) during the composting process is important for the removal of ARGs. In this study, three levels of tylosin (25, 50, and 75 mg kg(-1) on a dry weight basis) were added to swine manure plus a control, which was composted with cotton stalks. Each treatment was repeated in triplicate and the ARG profiles were determined with different levels of tylosin. The top 35 genera and ARGs profiles were clustered together based on the composting time. Combined composting parameters (temperature, pH, NH4+-N, NO3-N, and moisture content) accounted for 78.4% of the total variation in the changes in the potential host bacteria. In addition, the selected five composting parameters and six phyla (including 25 potential host bacterial genera) explained 46.9% and 30.7% of the variation in the ARG profiles according to redundancy analysis, respectively. The variations in ARGs during the composting process were mainly affected by the dynamics of potential host bacteria rather than integrons and the selective pressure due to bio-Cu and bio-Zn.