Purpose Remediation of polybrominated diphenyl ethers (PBDEs)/heavy metals/antibiotics mixed contaminated soil with high abundance of antibiotic resistance genes (ARGs) has being greatly challenging. Materials and methods An elevated soil washing procedure was developed to investigate the potential of applying DNA solution to extract PBDEs, Cu, Pb, tetracycline, and sulfadiazine from a high abundance of ARG-affected soil, followed by microbial augmentation to restore the microbiological functioning of washed soil. Results and discussion Two successive washings with 15 g L −1 DNA solution plus ultrasonication (25 kHz for 15 min) were optimal for extracting 80.6 % BDE28, 85.2 % BDE47, 64.7 % Cu, 60.3 % Pb, 100 % tetracycline, and 100 % sulfadiazine. Simultaneously, the ARG abundance decreased to the level of 10 −7 -10 −8 (ARGs copies/16S copies). Moreover, combined treatment with PBDE-degrading bacteria inoculation and nutrient application for 3 months to the second washed soil resulted in the further degradation of residual BDE28 and BDE47. Furthermore, the bacterial community composition was restored and the transfer risk of residual pollutants was limited, as indicated by high-throughput sequencing technology analysis and heavy metals stability model evaluation.Conclusions The combined cleanup technology is an environmentally friendly and effective technology to remediate mixed contaminated soils.