The inactivation of an isolated sulfonamide antibiotic resistant bacteria (ARB) HLS-6 and reduction of intracellular sul1 and intI1 in its genome by UVC irradiation, PMS oxidation and UVC-activated peroxymonosulfate (UVC/PMS) treatments were investigated in this study. The UVC/PMS treatment was superior to the other two methods in the inactivation of ARB and reduction of qPCR-sul1 and qPCR-intI1. The HLS-6 ARB (10(8) CFU/mL) could be effectively inactivated 5.3 log by UVC (100 mu W/cm(2))/PMS (1 mg/L), and the reduction rates of qPCR-sul1 and qPCR-intI1 by UVC (100 mu W/cm(2))/PMS (20 mg/L), reached up to 2.9 log and 3.4 log, respectively within 30 min. qPCR-intI1 reacted faster than qPCR-sul1 in all methods. Sulfate radical was responsible for the reduction of target genes, while hydroxyl radical had negligible effect on that. The dosage of PMS positively affected the reduction of both genes during UVC/PMS, while the initial concentration of ARB could negatively influence the reduction of target genes. The pH 5 of reaction solution was most beneficial to the reduction of ARGs. The reduction rates at pH 5 reached up to 3.1 log (sul1) and 3.3 log (intI1). The reduction of target genes was slightly facilitated in the initial 5 min and suppressed after 5 min with the co-existence of sulfamethoxazole. This study will provide a potential alternative method for controlling the antibiotic resistance in aquatic environment.